Npyy5 antagonists

ABSTRACT

The present invention provides a pharmaceutical composition for use as an NPY Y5 receptor antagonist comprising a compound of the formula (I):                    
     wherein R 1  is lower alkyl, cycloalkyl or the like, 
     R 2  is hydrogen, lower alkyl or the like, 
     n is 1 or 2, 
     X is lower alkylene, lower alkenylene, arylene, cycloalkylene or the like, 
     Y is CONR 7 , CSNR 7 , NR 7 CO, NR 7 CS or the like, 
     Z is lower alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl or the like and R 7  is hydrogen or lower alkyl, 
     prodrug, pharmaceutically acceptable salt or solvate thereof.

TECHNICAL FIELD

The present invention relates to a pharmaceutical composition for use asan NPY Y5 receptor antagonist, specifically, anti-obestic agent andnovel compounds having an anti-obestic activity.

BACKGROUND ART

Neuropeptide Y (hereinafter referred to as NPY) is a peptide whichconsists of 36 amino acid residues and was isolated from porcine brainin 1982. NPY is widely distributed in the central nervous system andperipheral tissues of humans and animals.

It has been reported that NPY possesses a stimulating activity of foodintake, an anti-seizure activity, a learning-promoting activity, ananti-anxiety activity, an anti-stress activity etc. in central nervoussystem, and it may be pivotally involved in the central nervous systemdiseases such as depression, Alzheimer's disease and Parkinson'sdisease. NPY is thought to be associated with the cardiovasculardiseases, since it induces a contraction of smooth muscles such as bloodvessels or cardiac muscles in the peripheral tissues. Furthermore, NPYis also known to be involved in the metabolic diseases such as obesity,diabetes, and hormone abnormalities (Trends in Pharmacological Sciences,Vol.15, and 153 (1994)). Therefore, an NPY receptor antagonist isexpected as a medicine for preventing or treating various diseasesinvolved in the NPY receptor.

Subtypes of Y1, Y2, Y3, Y4, Y5, and Y6 have now been identified as theNPY receptor (Trends in Pharmacological Sciences, Vol.18, and 372(1997)). It has been suggested that the Y5 receptor is at least involvedin the feeding behavior and its antagonist is expected as ananti-obestic agent (Peptides, Vol.18, and 445 (1997)).

Quinazoline compounds having similar structures to those of thecompounds of the present invention and exhibiting an NPY receptorantagonistic activity are described in WO97/20820, WO97/20821,WO97/20823 and the like. In addition, it is described that ureaderivatives having a sulfonamide group and amide derivatives having asulfonyl group in WO 99/64349 and benzyl sulfonamide derivatives inEP1010691-A, have an NPY antagonistic activity.

Compounds having similar structures to those of the compounds of thepresent invention are described in JP59-16871-A and WO97/15567. Theiractivities are quite different from that of the present invention andthese documents do not suggest the present invention.

DISCLOSURE OF INVENTION

The object of the present invention is to provide a superiorpharmaceutical composition for use as an NPY Y5 receptor antagonist andnovel compounds having the activity.

The present invention provides

[1] A pharmaceutical composition for use as an NPY Y5 receptorantagonist comprising a compound of the formula (I):

wherein R¹ is optionally substituted lower alkyl, optionally substitutedcycloalkyl or optionally substituted aryl,

R² is hydrogen or lower alkyl, and R¹ and R² taken together may formlower alkylene,

n is 1 or 2,

X is optionally substituted lower alkylene,

optionally substituted lower alkenylene,

optionally substituted —CO-lower alkylene,

optionally substituted —CO-lower alkenylene or

wherein R³, R⁴, R⁵and R⁶ are each independently hydrogen or lower alkyl,

is optionally substituted cycloalkylene, optionally substitutedcycloalkenylene, optionally substituted bicycloalkylene, optionallysubstituted arylene or optionally substituted heterocyclediyl and p andq are each independently 0 or 1,

—NR²—X— may be

 wherein

is piperidinediyl, piperazinediyl, pyridinediyl, pyrazinediyl,pyrrolidinediyl or pyrrolediyl and U is single bond, lower alkylene orlower alkenylene,

Y is OCONR⁷, CONR⁷, CSNR⁷, NR⁷CO or NR⁷CS,

R⁷ is hydrogen or lower alkyl, and

Z is optionally substituted lower alkyl, optionally substituted loweralkenyl, optionally substituted amino, optionally substituted loweralkoxy, optionally substituted carbocyclyle or optionally substitutedheterocyclyl,

prodrug, pharmaceutically acceptable salt or solvate thereof,

[2] The pharmaceutical composition for use as an NPY Y5 receptorantagonist described in [1] wherein R² is hydrogen or lower alkyl and Zis optionally substituted lower alkyl, optionally substituted loweralkenyl, optionally substituted lower alkoxy, optionally substitutedcarbocyclyl, optionally substituted heterocyclyl or optionallysubstituted amino, provided that R¹ is optionally substituted C3 to C10alkyl when Z is optionally substituted amino,

[3] The pharmaceutical composition for use as an NPY Y5 receptorantagonist described in [1] wherein R¹ is optionally substituted loweralkyl or optionally substituted cycloalkyl, X is optionally substitutedlower alkylene, optionally substituted lower alkenylene or

wherein

is the same as defined in [1], and Z is optionally substituted loweralkyl, optionally substituted carbocyclyl or optionally substitutedheterocyclyl,

[4] The pharmaceutical composition for use as an NPY Y5 receptorantagonist described in any one of [1] to [3] wherein R¹ is optionallysubstituted C3 to C10 alkyl,

[5] The pharmaceutical composition for use as an NPY Y5 receptorantagonist described in any one of [1] to [4] which is an anti-obesticagent,

[6] The pharmaceutical composition for use as an NPY Y5 receptorantagonist described in any one of [1] to [4] which is an anorecticagent,

[7] A method for treating and/or preventing obesity comprisingadministering an effective dose of an NPY Y5 receptor antagonistdescribed in any one of [1] to [4],

[8] A method for suppressing food intake comprising administering aneffective dose of an NPY Y5 receptor antagonist described in any one of[1] to [4],

[9] Use of an NPY Y5 receptor antagonist described in any one of [1] to[4] for manufacturing a medicine for treating and/or preventing obesity,

[10] Use of an NPY Y5 receptor antagonist described in any one of [1] to[4] for manufacturing a medicine for suppressing food intake,

[11] A compound of the formula (I):

wherein X is C2 to C6 alkylene or C3 to C6 alkenylene, R¹ is optionallysubstituted C3 to C10 alkyl or optionally substituted C5 to C6cycloalkyl and the other symbols are the same as defined in [1],provided that Z is not lower alkylphenylamino,

hydroxy(lower)alkylphenylamino and acylphenylamino when Y is NR⁷CO,

prodrug, pharmaceutically acceptable salt or solvate thereof,

[12] The compound described in [11] wherein Z is optionally substitutedlower alkyl or optionally substituted phenyl, prodrug, pharmaceuticallyacceptable salt or solvate thereof,

[13] A compound of the formula (I):

wherein X is

is optionally substituted cycloalkylene, optionally substitutedcycloalkenylene, optionally substituted bicycloalkylene or optionallysubstituted piperidinylene, R¹ is optionally substituted C3 to C10 alkylor optionally substituted C5 to C6 cycloalkyl and the other symbols arethe same as defined in [1], prodrug, pharmaceutically acceptable salt orsolvate thereof,

[14] The compound described in [13] wherein is optionally substitutedcyclohexylene or optionally substituted piperidinylene and p and q aresimultaneously 0, prodrug, pharmaceutically acceptable salt or solvatethereof,

[15] The compound described in [13] or [14] wherein Y is CONH, prodrug,pharmaceutically acceptable salt or solvate thereof,

[16] The compound described in any one of [13] to [15] wherein Z isoptionally substituted lower alkyl, optionally substituted phenyl,optionally substituted pyridyl or optionally substituted benzopyranyl,prodrug, pharmaceutically acceptable salt or solvate thereof,

[17] A compound of the formula (I):

wherein X is

R¹ is optionally substituted C3 to C10 alkyl or optionally substitutedC5 to C6 cycloalkyl,

Z is p-(lower)alkylphenyl and the other symbols are the same as definedin [1], provided that Z is not p-n-butylphenyl when R¹ is isopropyl,

prodrug, pharmaceutically acceptable salt or solvate thereof,

[18] A compound of the formula (I):

wherein X is

is heteroarylene, R¹ is optionally substituted C3 to C10 alkyl oroptionally substituted C5 to C6 cycloalkyl and the other symbols are thesame as defined in [1], prodrug, pharmaceutically acceptable salt orsolvate thereof,

[19] The compound described in [18] wherein

is thiophenediyl or furandiyl, prodrug, pharmaceutically acceptable saltor solvate thereof and

[20] A pharmaceutical composition comprising the compound described inany one of [11] to [19], prodrug, pharmaceutically acceptable salt orsolvate thereof.

BEST MODE FOR CARRYING OUT THE INVENTION

In the present specification, the term “halogen” includes fluorine,chlorine, bromine and iodine. Fluorine or chlorine is preferable.

The term “protective group” in “optionally protected hydroxy” and“optionally protected hydroxy(lower)alkyl” includes all of hydroxyprotecting groups usually used. For example, acyl such as acetyl,trichloroacetyl and benzoyl, lower alkoxycarbonyl such ast-butoxycarbonyl, lower alkylsulfonyl such as methane sulfonyl, loweralkoxy(lower)alkyl such as methoxymethyl, trialkylsilyl such ast-butyldimethylsilyl are included.

The term “lower alkyl” includes C1 to C10 straight or branched alkyl.The examples of “lower alkyl” are methyl, ethyl, n-propyl, isopropyl,n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl,neopentyl, hexyl, isohexyl, n-heptyl, isoheptyl, n-octyl, isooctyl,n-nonyl and n-decyl.

“Lower alkyl” represented by R¹ is preferably C3 to C10 alkyl, morepreferably C3 to C6 alkyl and most preferably isopropyl or t-butyl.

“Lower alkyl” in other cases is preferably C1 to C6 alkyl and morepreferably C1 to C4 alkyl.

The examples of substituents of “optionally substituted lower alkyl”represented by Z are, (1) halogen; (2) cyano;

(3) the following groups (i) to (xvi), which are optionally substitutedwith one or more substituents selected from “a substituents group β”defined below,

(i) hydroxy, (ii) lower alkoxy, (iii) mercapto, (iv) lower alkylthio,(v) acyl, (vi) acyloxy, (vii) carboxy, (viii) lower alkoxycarbonyl, (ix)imino, (x) carbamoyl, (xi) thiocarbamoyl, (xii) lower alkylcarbamoyl,(xiii) lower alkylthiocarbamoyl, (xiv) amino, (xv) lower alkylamino or(xvi) heterocyclylcarbonyl; or

(4) a group of the formula:

wherein R¹⁰ and R¹¹ are each independently hydrogen or lower alkyl andwhen this group has two or more of R¹⁰ and/or two or more of R¹¹, eachR¹⁰ and/or each R¹¹ may be different,

W is single bond, O, S or NR¹²,

R¹² is hydrogen, lower alkyl or phenyl,

is cycloalkyl, bicycloalkyl, cycloalkenyl, aryl or heterocyclyl, each ofwhich is optionally substituted with one or more of substituentsselected from “a substituents group α” defined below and

s is an integer of 0 to 4.

In the present specification, “a substituents group α” is a groupconstituting of (1) halogen; (2) oxo; (3) cyano; (4) nitro; (5) iminooptionally substituted with lower alkyl or hydroxy;

(6) the following groups (i) to (xxi), which are optionally substitutedwith one or more of groups selected from the substituents group A,

(i) hydroxy, (ii) lower alkyl, (iii) lower alkenyl, (iv) lower alkoxy,(v) carboxy, (vi) lower alkoxycarbonyl, (vii) acyl, (viii) acyloxy, (ix)imino, (x) mercapto, (xi) lower alkylthio, (xii) carbamoyl, (xiii) loweralkylcarbamoyl, (xiv) cycloalkylcarbamoyl, (xv) thiocarbamoyl, (xvi)lower alkylthiocarbamoyl, (xvii) lower alkylsulfinyl, (xviii) loweralkylsulfonyl, (xix) sulfamoyl, (xx) lower alkylsulfamoyl and (xxi)cycloalkylsulfamoyl;

(7) the following groups (i) to (v), which are optionally substitutedwith the substituents group β, lower alkyl, lower alkoxy(lower)alkyl,optionally protected hydroxy(lower)alkyl, halogeno(lower)alkyl, loweralkylsulfonyl and/or arylsulfonyl,

(i) cycloalkyl, (ii) cycloalkenyl, (iii) cycloalkyloxy, (iv) amino and(v) alkylenedioxy; and

(8) the following groups (i) to (xii), which are optionally substitutedwith the substituents group β, lower alkyl, halogeno(lower)alkyl and/oroxo,

(i) phenyl, (ii) naphthyl, (iii) phenoxy, (iv) phenyl(lower)alkoxy, (v)phenylthio, (vi) phenyl(lower)alkylthio, (vii) phenylazo, (viii)heterocyclyl, (ix) heterocyclyloxy, (x) heterocyclylthio, (xi)heterocyclylcarbonyl and (xii) heterocyclylsulfonyl.

The preferable examples of the substituents group α as substituents forB ring are halogen; nitro; hydroxy;

optionally substituted lower alkyl wherein the substituents is halogen,cyano, phenyl, carboxy and/or lower alkoxycarbonyl;

lower alkenyl; lower alkoxycarbonyl(lower)alkenyl;

optionally substituted lower alkoxy wherein the substituents is halogen,hydroxy, lower alkoxy, carboxy, lower alkoxycarbonyl, lower alkylaminoand/or cyano;

acyl; hydroxyimino; lower alkylthio; lower alkylsulfinyl; sulfamoyl;

optionally substituted amino wherein the substituents is lower alkyl,optionally protected hydroxy(lower)alkyl, phenyl and/or acyl;

alkylenedioxy; cyanophenyl; heterocyclylphenyl; biphenylyl; phenoxy;phenylazo optionally substituted with lower alkyl; or

optionally substituted heterocyclyl wherein the substituents isoptionally protected hydroxy, mercapto, halogen, lower alkyl,cycloalkyl, lower alkoxycarbonyl, amino, lower alkoxycarbonyl amino,carbamoyl, oxo, phenyl, lower alkoxyphenyl or heterocyclyl. Morepreferable examples are halogen; lower alkyl optionally substituted withhalogen; or lower alkoxy optionally substituted with halogen.

“A substituents group β” is a group consisting of halogen, optionallyprotected hydroxy, mercapto, lower alkoxy, lower alkenyl, amino, loweralkylamino, lower alkoxycarbonylamino, lower alkylthio, acyl, carboxy,lower alkoxycarbonyl, carbamoyl, cyano, cycloalkyl, phenyl, phenoxy,lower alkylphenyl, lower alkoxyphenyl, halogenophenyl, naphthyl andheterocyclyl.

Examples of the substituents for “optionally substituted lower alkyl”represented by any other than Z (e.g., R¹) are one or more substituentsselected from the substituents group β. The lower alkyl may besubstituted with these substituents at any possible positions.

The lower alkyl part in “lower alkoxy”, “lower alkoxycarbonyl”, “loweralkoxycarbonyl(lower)alkyl”, “lower alkylphenyl”, “lower alkoxyphenyl”,“lower alkylcarbamoyl”, “lower alkylthiocarbamoyl”, “lower alkylamino”,“halogeno(lower)alkyl”, “hydroxy(lower)alkyl”, “phenyl(lower)alkoxy”,“lower alkylthio”, “phenyl(lower)alkylthio”, “loweralkoxycarbonylamino”, “lower alkoxycarbonyl(lower)alkenyl”, “loweralkylsulfinyl”, “lower alkylsulfonyl”, “aryl(lower)alkoxycarbonyl”,“lower alkylbenzoyl” and “lower alkoxybenzoyl” is the same as defined inthe above “lower alkyl”.

Examples of substituents for “optionally substituted lower alkoxy” areone or more substituents selected from the substituents group β.Preferable examples are phenyl, lower alkylphenyl, lower alkoxyphenyl,naphthyl and heterocyclyl.

The term “cycloalkyl” includes C3 to C8 cyclic alkyl and preferably C5to C6 cyclic alkyl. Examples are cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl and cyclooctyl.

Examples of substituents for “optionally substituted cycloalkyl” are oneor more substituents selected from the substituents group α and thecycloalkyl may be substituted with these substituents at any possiblepositions.

The term “bicycloalkyl” includes a group which is formed by excludingone hydrogen from a C5 to C8 aliphatic cycle containing two rings whichpossess two or more of atoms in common. Examples arebicyclo[2.1.0]pentyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl andbicyclo[3.2.1]octyl.

The term “lower alkenyl” includes C2 to C10, preferably C2 to C8 andmore preferably C3 to C6 straight or branched alkenyl having one or moredouble bonds at any possible positions. Examples are vinyl, propenyl,isopropenyl, butenyl, isobutenyl, phenyl, butadienyl, pentenyl,isopentenyl, pentadienyl, hexenyl, isohexenyl, hexadienyl, heptenyl,octenyl, nonenyl and decenyl.

The “lower alkenyl” part in “lower alkoxycarbonyl(lower)alkenyl” is thesame as the above “lower alkenyl”.

Examples of the substituents for “optionally substituted lower alkenyl”are halogen, lower alkoxy, lower alkenyl, amino, lower alkylamino, loweralkoxycarbonylamino, lower alkylthio, acyl, carboxy, loweralkoxycarbonyl, carbamoyl, cyano, cycloalkyl, phenyl, lower alkylphenyl,lower alkoxyphenyl, naphthyl and/or heterocyclyl.

The term “acyl” includes (1) C1 to C10, preferably C1 to C6 and morepreferably C1 to C4 straight or branched alkylcarbonyl oralkenylcarbonyl, (2) C4 to C9 and preferably C4 to C7 cycloalkylcarbonyland (3) C7 to C11 arylcarbonyl. Examples are formyl, acetyl, propionyl,butyryl, isobutyryl, valeryl, pivaloyl, hexanoyl, acryloyl, propioloyl,methacryloyl, crotonoyl, cyclopropylcarbonyl, cyclohexylcarbonyl,cyclooctylcarbonyl and benzoyl.

The “acyl” part in “acyloxy” is the same as the above.

The term “cycloalkenyl” includes a group having at least one double bondat any possible positions in the above cycloalkyl. Examples arecyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl andcyclohexadienyl.

Examples of substituents for “optionally substituted cycloalkenyl” areone or more substituents selected from the substituents group β.

Examples of substituents for “optionally substituted amino” are thesubstituents group β, optionally substituted benzoyl and/or optionallysubstituted heterocyclylcarbonyl wherein the substituents is hydroxy,lower alkyl, lower alkoxy and/or lower alkylthio.

The term “aryl” includes a monocyclic of polycyclic aromatic carbocyclylgroup and examples are phenyl, naphthyl, anthryl and phenanthryl. “Aryl”includes aryl fused with other a non-aromatic carbocyclyl group, forexample, indanyl, indenyl, biphenylyl, acenaphthyl, tetrahydronaphthyland fluorenyl. Phenyl is preferable.

The aryl part in “aryl lower alkoxycarbonyl” is the same as the above.

The term “optionally substituted aryl” and “optionally substitutedphenyl” represented by Z include the above “aryl” and “phenyl”respectively, which may be substituted with the substituents group α orlower alkyl which may be substituted with one or more group selectedfrom the substituents group α.

Examples of the substituents for “optionally substituted aryl” and“optionally substituted phenyl” represented by any other than Z are oneor more groups selected from the substituents group β.

The term “carbocyclyl” includes the above “cycloalkyl”, “cycloalkenyl”,“bicycloalkyl” and “aryl”.

The term “non-aromatic carbocyclyl” includes the above “cycloalkyl”,“cycloalkenyl” and “bicycloalkyl”.

The term “optionally substituted carbocyclyl” includes the above“optionally substituted cycloalkyl”, “optionally substitutedcycloalkenyl”, “optionally substituted bicycloalkyl” and “optionallysubstituted aryl”.

The term “heterocyclyl” includes a heterocyclic group containing atleast one heteroatom arbitrarily selected from O, S and N. For example,5- or 6-membered heteroaryl such as pyrrolyl, imidazolyl, pyrazolyl,pyridyl, pyridazinyl, pyrimidinyl, oxazolyl, oxadiazolyl, isothiazolyl,thiazolyl, thiadiazolyl, furyl and thienyl; fused heterocyclylconsisting of two rings such as indolyl, isoindolyl, indazolyl,indolizinyl, indolinyl, isoindolinyl, quinolyl, isoquinolyl, cinnolinyl,phthalazinyl, quinazolinyl, naphthyridinyl, quinoxalinyl, purinyl,pteridinyl, benzopyranyl, benzimidazolyl, benzisoxazolyl, benzoxazolylbenbzoxadiazolyl, benzisothiazolyl, benzothiazolyl, benzothiadiazolyl,benzofuryl, isobenzofuryl, benzothienyl, benzotriazolyl, imidazopyridyl,triazoropyridyl, imidazothiazolyl, pyrazinopyridazinyl, quinazolinyl,quinolyl, isoquinolyl, naphthyridinyl, dihydropyridyl,tetrahydroquinolyl and tetrahydrobenzothienyl; fused heterocyclylconsisting of three rings such as carbazolyl, acridinyl, xanthenyl,phenothiazinyl, phenoxathiinyl, phenoxazinyl and dibenzofuryl; andnon-aromatic heterocyclyl such as dioxanyl, thiiranyl, oxiranyl,oxathiolanyl, azetidinyl, thianyl, pyrrolidinyl, pyrrolinyl,imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidyl,piperazinyl, morpholinyl, morpholino, thiomorpholinyl, thiomorpholino,dihydropyridyl, tetrahydrofuryl, tetrahydropyranyl, tetrahydrothiazolyland tetrahydroisothiazolyl.

“Fused heterocyclyl” fused with a ring other than a heterocycle (e.g.,benzothiazolyl), may connect at any possible position.

Substituents for “optionally substituted heterocyclyl” are the same asthose for the above “optionally substituted aryl”.

Heterocyclyl parts in “heterocyclylcarbonyl”, “heterocyclyloxy”,“heterocyclylthio” and “heterocyclyl substituted phenyl” are the same asthe above “heterocyclyl”.

The term “lower alkylene” includes a bivalent group comprising 1 to 6 ofmethylene, preferably 2 to 6 of methylene and more preferably 3 to 6 ofmethylene. For example, methylene, ethylene, trimethylene,tetramethylene, pentamethylene and hexamethylene are included.Tetramethylene is preferable.

“R¹ and R² taken together may form lower alkylene” includes the case

Preferable examples are

Lower alkylene part in “lower alkylenedioxy” is the same as the above“lower alkylene”. Methylenedioxy or ethylenedioxy is preferable.

The term “lower alkenylene” includes a bivalent group comprising 2 to 6of methylene, preferably 3 to 6 of methylene and more preferably 4 to 5of methylene and including at least one double bond.

The term “cycloalkylene” includes a bivalent group which is formed byexcluding one hydrogen from the above “cycloalkyl”. A preferable exampleof cycloalkylene represented by X is 1,4-cyclohexanediyl.

The term “cycloalkenylene” includes a group containing at least onedouble bonds in the above cycloalkylene.

The term “bicycloalkylene” includes a group which is formed by excludingone hydrogen from the above “bicycloalkyl”. Examples arebicyclo[2.1.0]pentylene, bicyclo[2.2.1]heptylene,bicyclo[2.2.2]octylene, and bicyclo[3.2.1]octylene.

The term “heterocyclediyl” includes a bivalent group which is formed byexcluding one hydrogen from the above “heterocyclyl”. Piperidinediyl,piperazinediyl, pyridinediyl, pyrimidinediyl, pyrazinediyl,pyrrolidinediyl or pyrrolediyl is preferable and piperidindiyl is morepreferable.

The term “arylene” includes a bivalent group which is formed byexcluding one hydrogen from the above “aryl”. Phenylene is preferable.

The term “heteroarylene” includes aromatic groups in the above“heterocyclediyl”. Examples are pyrrolediyl, imidazolediyl,pyrazolediyl, pyridinediyl, pyridazinediyl, pyrimidinediyl,pyrazinediyl, triazolediyl, triazinediyl, isoxazolediyl, oxazolediyl,oxadiazolediyl, isothiazolediyl, thiazolediyl, thiadiazolediyl,furandiyl and thiophenediyl.

One or more groups selected from the substituents group β are examplesof substituents for “optionally substituted lower alkylene”, “optionallysubstituted lower alkenylene”, “optionally substituted cycloalkylene”,“optionally substituted cyclohexylene”, “optionally substitutedbicycloalkylene”, “optionally substituted cycloalkenylene”, “optionallysubstituted phenylene”, “optionally substituted heterocyclediyl” and“optionally substituted piperidinylene”. Halogen, hydroxy, lower alkyl,halogeno(lower)alkyl, lower alkoxy, amino, lower alkylamino, acyl,carboxy or lower alkoxycarbonyl is preferable. These substituents mayattach to any possible positions.

When —NR²—X— is

U is preferably single bond or methylene. More preferably,

is

The compounds of the present invention include any formable andpharmaceutically acceptable salts thereof. Examples of “thepharmaceutically acceptable salt” are salts with mineral acids such ashydrochloric acid, sulfuric acid, nitric acid and phosphoric acid; saltswith organic acids such as para-toluenesulfonic acid, methanesulfonicacid, oxalic acid and citric acid; salts with organic bases such asammonium, trimethylammonium and triethylammonium; salts with alkalinemetals such as sodium and potassium; and salts with alkaline earthmetals such as calcium and magnesium.

The compounds of the present invention include solvates thereof. Hydrateis preferable and arbitrary numbers of water molecules may coordinate tothe compound of the present invention.

The compounds of the present invention include prodrugs thereof. Prodrugincludes derivatives of the compounds of the present invention whichhave a chemically or metabolically decomposable group and can beconverted into pharmaceutically active compounds of the presentinvention in vivo by solvolysis or under the physiological conditions.The methods for selecting and producing suitable prodrugs are describedin Design of Prodrugs, Elsevier, Amsterdam 1985.

When a compound (I) of the present invention has carboxy, examples ofprodrugs are an ester derivative and an amide derivative, which can beproduced by reacting a compound (I) having carboxy with a suitablealcohol or a suitable amine, respectively.

When a compound (I) of the present invention has hydroxy, an example ofprodrugs is an acyloxy derivative, which can be synthesized by reactinga compound (I) having hydroxy with a suitable acyl halide or a suitableacid anhydride.

When a compound (I) of the present invention has amino, an example ofprodrugs is an amide derivative, which can be synthesized by reacting acompound (I) having amino with a suitable acid halide or a suitablemixed acid anhydride.

When the compound (I) of the present invention has an asymmetric carbonatom, it includes racemates, all of enantiomers and all of stereoisomerssuch as diastereomer, epimer and enantiomer thereof.

When the compound (I) of the present invention having one or more doublebonds forms an E isomer or Z isomer, the compound (I) includes bothisomers. When X is cycloalkylene, the compound (I) includes both of cisisomer and trans isomer.

For example, the compound (I) of the present invention can besynthesized by the following methods.

(Compounds Wherein Y=CONR⁷)

wherein Hal is halogen, Q is an amino protecting group and the othersymbols are the same as the above.

Step A

Compound 1 is reacted with Amino Compound 2 having the desiredsubstituent Z and R⁷ in a suitable solvent at 0° C. to 50° C. forseveral minutes to several hours. As solvents, tetrahydrofuran,dimethylformamide, diethyl ether, dichloromethane, toluene, benzene,xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate,pentane, heptane, dioxane, acetone, acetonitrile, water, a mixturethereof etc. can be used. An activator such as thionyl chloride, acidhalide, acid anhydride and activated ester can be used, if necessary.

Step B

Compound 3 is deprotected by the usual method and reacted with SulfonylHalide 4 having the desired substituent R¹ in a suitable solvent at 0°C. to 50° C. for several minutes to several hours to give Compound (I-A)wherein n is 2. Tetrahydrofuran, dimethylformamide, diethyl ether,dichloromethane, toluene, benzene, xylene, cyclohexane, hexane,chloroform, ethyl acetate, butyl acetate, pentane, heptane, dioxane,acetone, acetonitrile, water and the mixture thereof etc. can be used asa solvent.

Step C

Compound (I-B) wherein n is 1 can be synthesized by reacting Compound 3with Sulfinyl Halide 5 having substituent R¹. The conditions for thereaction are the same as those of the above Step B.

Step D

Compound (I-B) obtained in Step C is oxidized by the usual method togive Compound (I-A) wherein n is 2. m-Chloroperbenzoic acid, peraceticacid, hydrogen peroxide, trifluoroperacetic acid, sodium periodate,sodium hypochlorite, potassium permanganate etc. can be used as anoxidizer and the reaction may be carried out at 0° C. to 50° C. Examplesof solvents are tetrahydrofuran, dimethylformamide, diethyl ether,dichloromethane, toluene, benzene, xylene, cyclohexane, hexane,chloroform, ethyl acetate, butyl acetate, pentane, heptane, dioxane,acetone, acetonitrile, water, methanol, ethanol, isopropanol and mixturethereof.

In case X is heterocyclediyl containing at least one N atom and the Natom connects to CONR⁷—Z in the compound (I), the following reaction maybe employed to obtain Compound (I-A′) or (I-B′). Step D may be carriedout just after Step C or Step E.

wherein R is lower alkyl or aryl and L is a leaving group.

Step C

Compound 5 is reacted with Compound 6 in a similar manner to the aboveStep C to give Compound 7.

Step E

Thus obtained Compound 7 is treated with a base in a suitable solvent togive Compound 8. For example, barium hydroxide, sodium hydroxide,potassium hydroxide, hydrazine or lithium propanethiolate can be used asa base. As a solvent, tetrahydrofuran, dimethylformamide, dioxane,acetone, acetonitrile, methanol, ethanol, propanol, water, the mixturethereof or the like can be used. The reaction can be carried out at 0°C. to 100° C. for several minutes to several tens hours.

Step F

Compound 8 is reacted with Compound 9 having a leaving group and adesired substituent in a suitable solvent in the presence or absence ofa base at 0° C. to 100° C. for several minutes to several days to giveCompound (I-B′). Examples of the leaving group are phenoxy, chloro andtrichloromethyl. Examples of the base are triethylamine, pyridine,diisopropylethylamine, sodium hydroxide, potassium carbonate and sodiumhydrogencarbonate. Examples of the solvent are tetrahydrofuran,dimethylformamide, diethyl ether, dichloromethane, toluene, benzene,xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate,pentane, heptane, dioxane, acetone, acetonitrile, methanol, ethanol andthe mixture thereof.

Step D

Compound (I-B′) is reacted in a similar manner to the above Step D togive Compound (I-A′).

(Compound Wherein Y=NR⁷CO)

wherein each of the symbols is the same as the above.

Step G and Step B

Compound 10 is reacted with Compound 11 under the same reactioncondition as that in Step B. Thus obtained Compound 12 is reacted in asimilar manner to the above Step B to give Compound (I-C) wherein n=2.

Step C and Step D

To synthesize Compound (I-D), Compound 12 obtained in Step G may bereacted in similar manners to the above Step C and Step D.

(Compound Wherein Y=OCONR⁷)

wherein each of symbols is the same as the above.

Step H

Compound 13 is reacted with Isocianate Compound 14 having a substituentZ in a suitable solvent in the presence or absence of a suitablecatalyst at 0° C. to 100° C. for several minutes to several days to giveCompound 15. Examples of the solvent are tetrahydrofuran,dimethylformamide, diethyl ether, dichloromethane, toluene, benzene,xylene, cyclohexane, hexane, chloroform, ethyl acetate, butyl acetate,pentane, heptane, dioxane, acetone, acetonitrile and the mixturethereof.

Step C and Step D

Thus obtained Compound 15 is reacted in similar manners to Step C andStep D to give Compound (I-E) of the present invention.

(Compound Wherein Y=CSNR⁷ or NR⁷CS)

Compound (I) wherein Y is CSNR⁷ or NR⁷CS can be synthesized by reactingCompound (I) wherein Y is CONR⁷ or NR⁷CO synthesized in any one of theabove methods with the Lawesson's reagent or phosphorus pentasulfide ina suitable solvent at 30° C. to 100° C. for several minutes to severalhours. Examples of the solvent are tetrahydrofuran, dimethylformamide,diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane,hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane,dioxane, acetone, acetonitrile and the mixture thereof.

Amino groups may be protected with a suitable protecting group in theusual manner at a suitable step. For example, phthalimide, loweralkoxycarbonyl, lower alkenyloxycarbonyl, halogenoalkoxycarbonyl,aryl(lower)alkoxycarbonyl, trialkylsilyl, lower alkylsulfonyl,halogeno(lower)alkylsulfonyl, arylsulfonyl, lower alkylcarbonyl andarylcarbonyl can be used as the protecting group.

After protection of the amino group, the compound is subjected to theabove-mentioned reactions and the obtained compound is deprotected bytreatment of an acid or a base in a suitable solvent at a suitablestage. Examples of a solvent is tetrahydrofuran, dimethylformamide,diethyl ether, dichloromethane, toluene, benzene, xylene, cyclohexane,hexane, chloroform, ethyl acetate, butyl acetate, pentane, heptane,dioxane, acetone, acetonitrile and the mixture thereof. Examples of abase are hydrazine, pyridine, sodium hydroxide and potassium hydroxideand examples of an acid are hydrochloric acid, trifluoroacetic acid andhydrofluoric acid.

All of the compounds of the present invention have an NPY Y5antagonistic activity and the following compounds are specificallypreferable.

In the formula (I),

a compound wherein R¹ is optionally substituted lower alkyl oroptionally substituted cycloalkyl (hereinafter referred to as “R¹ isR1-1”),

a compound wherein R¹ is C3 to C10 alkyl or C5 to C6 cycloalkyl, each ofwhich is optionally substituted with halogen (hereinafter referred to as“R¹ is R1-2”),

a compound wherein R¹ is C3 to C10 alkyl optionally substituted withhalogen (hereinafter referred to as “R¹ is R1-3”),

a compound wherein R¹ is isopropyl or t-butyl (hereinafter referred toas “R¹ is R1-4”),

a compound wherein R² is hydrogen or C1 to C3 alkyl (hereinafterreferred to as “R² is R2-1”),

a compound wherein R² is hydrogen (hereinafter referred to as “R² isR2-2”),

a compound wherein X is optionally substituted lower alkylene,optionally substituted lower alkenylene or

 wherein

is optionally substituted cycloalkylene, optionally substitutedcycloalkenylene, optionally substituted bicycloalkylene, optionallysubstituted phenylene or optionally substituted heterocyclediyl(hereinafter referred to as “X is X-1”),

a compound wherein X is C2 to C6 alkylene, C3 to C6 alkenylene or

 wherein

is optionally substituted cycloalkylene, optionally substitutedcycloalkenylene, optionally substituted bicycloalkylene, optionallysubstituted phenylene, optionally substituted piperidinylene, optionallysubstituted thiophenediyl or optionally substituted furandiyl(hereinafter referred to as “X is X-2”),

a compound wherein X is C2 to C6 alkylene or

 wherein is optionally substituted cycloalkylene, optionally substitutedphenylene, optionally substituted piperidinylene, optionally substitutedthiophenediyl or optionally substituted furandiyl (hereinafter referredto as “X is X-3”),

a compound wherein X is (i) C2 to C6 alkylene or (ii) cycloalkylene orphenylene, each of which is optionally substituted with halogen,hydroxy, lower alkyl or halogeno(lower)alkyl (hereinafter referred to as“X is X-4”),

a compound wherein X is C2 to C6 alkylene or to C5 to C6 cycloalkylene(hereinafter referred to as “X is X-5”),

a compound wherein X is C3 to C6 alkylene or 1,4-cyclohexylene(hereinafter referred to as “X is X-6”),

a compound wherein Y is CONR⁷, CSNR⁷, NR⁷CO or NR⁷CS and R⁷is hydrogenor C1 to C3 alkyl (hereinafter referred to as “Y is Y-1”),

a compound wherein Y is CONH, CSNH or NHCO (hereinafter referred to as“Y is Y-2”),

a compound wherein Y is CONH (hereinafter referred to as “Y is Y-3”),

a compound wherein Z is optionally substituted lower alkyl, optionallysubstituted carbocyclyl or optionally substituted heterocyclyl(hereinafter referred to as “Z is Z-1”),

a compound wherein Z is —(CR⁸R⁹)r-W—(CR¹⁰R¹¹)s-V

wherein R⁸, R⁹, R¹⁰ and R¹¹ are each independently hydrogen or loweralkyl and when Z has two or more of R⁸, two or more of R⁹, two or moreof R¹⁰ and/or two or more of R¹¹, each of R⁸, R⁹, R¹⁰ and R¹¹ may bedifferent, W is single bond, O, S or NR¹², R¹² is hydrogen, lower alkylor phenyl, V is hydrogen, optionally substituted cycloalkyl, optionallysubstituted bicycloalkyl, optionally substituted aryl or optionallysubstituted heterocyclyl, r is an integer of 1 to 4 and s is an integerof 0 to 4

(hereinafter referred to as “Z is Z-2”),

a compound wherein Z is —(CH2)r-W—(CH₂)s-V

wherein W is single bond, O, S or NR¹², R¹² is hydrogen or lower alkyl,V is optionally substituted aryl or optionally substituted heterocyclylwherein the substituents is halogen, hydroxy, lower alkyl,halogeno(lower)alkyl, lower alkoxy, lower alkenyl, amino, loweralkylamino, acyl, carboxy, lower alkoxycarbonyl, phenyl or monocyclicheteroaryl, r is an integer of 1 to 4 and s is an integer of 0 to 4

(hereinafter referred to as “Z is Z-3),

a compound wherein Z is —(CH₂)r-W—(CH2)s-V

wherein W is single bond, O, S, NH or NMe, V is optionally substitutedphenyl or optionally substituted heteroaryl wherein the substituents ishalogen, lower alkyl, halogeno(lower)alkyl, lower alkoxy, amino or loweralkylamino, r is an integer of 1 to 3 and s is an integer of 0 or 1

(hereinafter referred to as “Z is Z-4”),

a compound wherein Z is optionally substituted carbocyclyl,

wherein the substituent is halogen; hydroxy;

optionally substituted lower alkyl wherein the substituents is halogen,hydroxy, carboxy, lower alkoxycarbonyl, cyano and/or phenyl;

lower alkenyl optionally substituted with lower alkoxycarbonyl;

optionally substituted lower alkoxy wherein the substituents is halogen,hydroxy, lower alkoxy, carboxy, lower alkoxycarbonyl, lower alkylamino,cycloalkyl, cyano and/or heterocyclyl;

cycloalkyl; cycloalkyloxy; acyl; lower alkylthio; carbamoyl; loweralkylcarbamoyl; cycloalkylcarbamoyl; hydroxy imino;

optionally substituted amino wherein the substituents is lower alkyl,optionally protected hydroxy(lower)alkyl, lower alkoxy(lower)alkyl,acyl, lower alkylsulfonyl, arylsulfonyl and/or phenyl;

phenyl optionally substituted with halogen, cyano, phenyl and/orheterocyclyl;

lower alkylsulfinyl; lower alkylsulfamoyl; cycloalkylsulfamoyl;

nitro; cyano; alkylenedioxy; phenylazo optionally substituted with loweralkyl; phenoxy; oxo;

optionally substituted heterocyclyl wherein the substituents isoptionally protected hydroxy, mercapto, halogen, lower alkyl,cycloalkyl, lower alkoxycarbonyl, acyl, amino, loweralkoxycarbonylamino, carbamoyl, oxo, phenyl, lower alkoxyphenyl,halogenophenyl, heterocyclyl and/or oxo;

heterocyclylsulfonyl optionally substituted with lower alkyl;heterocyclyloxy; heterocyclylcarbonyl optionally substituted with loweralkyl

(hereinafter referred to as “Z is Z-5),

a compound wherein Z is optionally substituted phenyl

wherein the substituents is halogen; hydroxy; lower alkyl optionallysubstituted with halogen, hydroxy, lower alkoxycarbonyl, cyano and/orphenyl; lower alkoxycarbonyl(lower)alkenyl; lower alkoxy optionallysubstituted with halogen, lower alkoxy, lower alkoxycarbonyl, cycloalkyland/or heterocyclyl; cycloalkyl; cycloalkyloxy; acyl; lower alkylthio;carbamoyl; lower alkycarbamoyl; amino optionally substituted with loweralkyl, hydroxy(lower)alkyl, acyl, lower alkylsulfonyl and/or phenyl;phenyl optionally substituted with halogen, cyano, phenyl and/orheterocyclyl;

lower alkyl sulfamoyl; cycloalkylsulfamoyl; nitro; alkylenedioxy;phenylazo optionally substituted with lower alkyl; phenoxy; oxo;

heterocyclyl optionally substituted with hydroxy, halogen, lower alkyl,lower alkoxycarbonyl, amino, carbamoyl, phenyl, halogenophenyl,heterocyclyl and/or oxo;

heterocyclyloxy; and/or heterocyclylsulfonyl optionally substituted withlower alkyl

(hereinafter referred to as “ Z is Z-6”),

a compound wherein Z is optionally substituted phenyl

wherein the substituents is halogen; lower alkyl optionally substitutedwith halogen, hydroxy, lower alkoxycarbonyl and/or phenyl; lower alkoxyoptionally substituted with halogen and/or cycloalkyl; cycloalkyl;cycloalkyloxy; acyl; lower alkylthio; lower alkylcarbamoyl; aminooptionally substituted with lower alkyl, hydroxy(lower)alkyl, acyland/or phenyl; phenyl optionally substituted with piperidyl;cycloalkylsulfamoyl; alkylenedioxy; phenoxy;

morpholinyl or morpholino, each of which is optionally substituted withlower alkyl; piperidyl optionally substituted with hydroxy, lower alkyl,lower alkoxycarbonyl, phenyl, halogenophenyl and/or oxo; pyrrolidinyloptionally substituted with hydroxy, carbamoyl and/or oxo;

piperazinyl optionally substituted with phenyl or pyrimidinyl;dihydropyridyl; pyrrolyl; pyrrolinyl; imidazolyl optionally substitutedwith halogen and/or lower alkyl; pyrazolyl; thienyl; thiadiazolyl;furyl; oxazolyl; isoxazolyl; tetrazolyl optionally substituted withlower alkyl and/or phenyl; indolinyl; indolyl; tetrahydroquinolyl;benzothiazolyl optionally substituted with lower alkyl;tetrahydroisothiazolyl optionally substituted with oxo; benzopyranyloptionally substituted with oxo; tetrahydropyranyloxy;tetrahydrofuryloxy; morpholinosulfonyl optionally substituted with loweralkyl; and/or piperidylsulfonyl optionally substituted with lower alkyl

(hereinafter referred to as “Z is Z-7”),

a compound wherein Z is optionally substituted phenyl

wherein the substituents is halogen, lower alkyl, halogeno(lower)alkyl,lower alkoxy, cycloalkyloxy, lower alkylcarbamoyl, phenyl, lower alkylmorpholino and/or tetrahydropyranyloxy

(hereinafter referred to as “Z is Z-8”),

a compound wherein Z is optionally substituted heterocyclyl

wherein the substituents is halogen, hydroxy, lower alkyl,halogeno(lower)alkyl, lower alkoxy, mercapto, lower alkylthio, acyl,carboxy, lower alkoxycarbonyl, amino, lower alkylamino, phenyl,naphthyl, phenylthio optionally substituted with halogen, phenoxyoptionally substituted with halogen, oxo, and/or heterocyclyl optionallysubstituted with lower alkyl

(hereinafter referred to as “Z is Z-9”),

a compound wherein Z is thienyl, pyrazolyl, thiazolyl, thiadiazolyl,pyridyl, pyrimidinyl, pyrazinyl, triazinyl, indolyl, isoindolyl,indolinyl, isoindolinyl, indazolyl, benzopyranyl, benzoxazolyl,benzothienyl, benzothiazolyl, benzothiazolinyl, benzothiadiazolyl,quinolyl, isoquinolyl, dihydrobenzofuryl, carbazolyl, acridinyl ordibenzofuryl, each of which is optionally substituted with substituentsselected from the group of lower alkyl;

halogeno(lower)alkyl; lower alkoxy; lower alkoxycarbonyl; acyl; loweralkoxycarbonyl(lower)alkyl; mercapto; phenyl, naphthyl, phenylthio orphenoxy, each of which is optionally substituted with halogen; furyl;nitro; oxo; and morpholino optionally substituted with lower alkyl)(hereinafter referred to as “Z is Z-10”),

a compound wherein Z is thienyl, thiazolyl, thiadiazolyl, pyridyl,pyrazinyl, indolyl, isoindolinyl, benzopyranyl, quinolyl, carbazolyl,dibenzofuryl, benzopyranyl, benzothienyl or benzothiazolyl, each ofwhich is optionally substituted with one or more substituents selectedfrom the group of lower alkyl, halogeno(lower)alkyl, lower alkoxy, loweralkoxycarbonyl, acyl, phenyl, naphthyl, phenylthio, lower alkylmorpholino and oxo) (hereinafter referred to as “Z is Z-11),

a compound wherein R¹ is R1-2, R² is R2-2, n is 2 and a combination ofX, Y and Z, i.e., (X, Y, Z), is any one of the followings.

(X, Y, Z)=(X-3, Y-2, Z-1), (X-3, Y-2, Z-2), (X-3, Y-2, Z-3), (X-3, Y-2,Z-4), (X-3, Y-2, Z-5), (X-3, Y-2, Z-6), (X-3, Y-2, Z-7), (X-3, Y-2,Z-8), (X-3, Y-2, Z-9), (X-3, Y-2, Z-10), (X-3, Y-2, Z-11), (X-3, Y-3,Z-1), (X-3, Y-3, Z-2), (X-3, Y-3, Z-3), (X-3, Y-3, Z-4), (X-3, Y-3,Z-5), (X-3, Y-3, Z-6), (X-3, Y-3, Z-7), (X-3, Y-3, Z-8), (X-3, Y-3,Z-9), (X-3, Y-3, Z-10), (X-3, Y-3, Z-11), (X-4, Y-2, Z-1), (X-4, Y-2,Z-2), (X-4, Y-2, Z-3), (X-4, Y-2, Z-4), (X-4, Y-2, Z-5), (X-4, Y-2,Z-6), (X-4, Y-2, Z-7), (X-4, Y-2, Z-8), (X-4, Y-2, Z-9), (X-4, Y-2,Z-10), (X-4, Y-2, Z-11), (X-4, Y-3, Z-1), (X-4, Y-3, Z-2), (X-4, Y-3,Z-3), (X-4, Y-3, Z-4), (X-4, Y-3, Z-5), (X-4, Y-3, Z-6), (X-4, Y-3,Z-7), (X-4, Y-3, Z-8), (X-4, Y-3, Z-9), (X-4, Y-3, Z-10), (X-4, Y-3,Z-11), (X-5, Y-2, Z-1), (X-5, Y-2, Z-2), (X-5, Y-2, Z-3), (X-5, Y-2,Z-4), (X-5, Y-2, Z-5), (X-5, Y-2, Z-6), (X-5, Y-2, Z-7), (X-5, Y-2,Z-8), (X-5, Y-2, Z-9), (X-5, Y-2, Z-10), (X-5, Y-2, Z-11), (X-5, Y-3,Z-1), (X-5, Y-3, Z-2), (X-5, Y-3, Z-3), (X-5, Y-3, Z-4), (X-5, Y-3,Z-5), (X-5, Y-3, Z-6), (X-5, Y-3, Z-7), (X-5, Y-3, Z-8), (X-5, Y-3,Z-9), (X-5, Y-3, Z-10), (X-5, Y-3, Z-11),

the pharmaceutically acceptable salt, solvate or prodrug thereof.

The NPY Y5 receptor antagonist of the present invention is effective forall of the diseases in which NPY Y5 is involved and it is especiallyuseful for preventing and/or treating obesity and suppressing foodintake. Moreover, the antagonist is effective for preventing and/ortreating the diseases in which obesity acts as a risk factor, forexample, diabetes, hypertension, hyperlipemia, atherosclerosis and acutecoronary syndrome.

In addition, the NPY Y5 receptor antagonist of the present invention hasa low affinity for NPY Y1 and Y2 receptors, and has a high selectivityfor NPY Y5 receptor. NPY causes a sustained vasoconstrictive action inthe periphery and this action is mainly via Y1 receptor. Since Y5receptor is not involved in this action at all, the NPY Y5 receptorantagonist has a low risk of inducing side effects based on theperipheral vasoconstriction, and is expected to be suitably used as asafe medicine.

The NPY Y5 receptor antagonist shows an anti-obestic effect bysuppressing food intake. Therefore, it is one of the features that thisantagonist does not induce side effects, e.g., an indigestion caused byan anti-obestic agent which inhibits digestion and absorption, and acentral side effect such as anti-depression caused by a serotonintransporter inhibitor showing an anti-obesity effect.

A compound of the present invention can be administered orally orparenterally as an anti-obestic agent or anorectic agent. In the case oforal administration, it may be in any usual form such as tablets,granules, powders, capsules, pills, solutions, syrups, buccal tabletsand sublingual tablets. When the compound is parenterally administered,any usual form is preferable, for example, injections (e.g.,intravenous, intramuscular), suppositories, endermic agents and vapors.Oral administration is particularly preferable because the compounds ofthe present invention show a high oral absorbability.

A pharmaceutical composition may be manufactured by mixing an effectiveamount of a compound of the present invention with variouspharmaceutical additives suitable for the administration form, such asexcipients, binders, moistening agents, disintegrators, lubricants anddiluents. When the composition is of an injection, an active ingredienttogether with a suitable carrier can be sterilized to give apharmaceutical composition.

Examples of the excipients include lactose, saccharose, glucose, starch,calcium carbonate and crystalline cellulose. Examples of the bindersinclude methylcellulose, carboxymethylcellulose, hydroxypropylcellulose,gelatin and polyvinylpyrrolidone. Examples of the disintegrators includecarboxymethylcellulose, sodium carboxymethylcellulose, starch, sodiumalginate, agar and sodium lauryl sulfate. Examples of the lubricantsinclude talc, magnesium stearate and macrogol. Cacao oil, macrogol,methylcellulose etc. may be used as base materials of suppositories.When the composition is manufactured as solutions, emulsified injectionsor suspended injections, dissolving accelerators, suspending agents,emulsifiers, stabilizers, preservatives, isotonic agents and the likemay be added. For oral administration, sweetening agents, flavors andthe like may be added.

Although the dosage of a compound of the present invention as ananti-obestic agent or anorectic agent should be determined inconsideration of the patient's age and body weight, the type and degreeof diseases, the administration route etc., a usual oral dosage for anadult is 0.05 to 100 mg/kg/day and preferable is 0.1 to 10 mg/kg/day.For parenteral administration, although the dosage highly varies withadministration routes, a usual dosage is 0.005 to 10 mg/kg/day,preferably, 0.01 to 1 mg/kg/day. The dosage may be administered in oneto several divisions per day.

The present invention is further explained by the following Examples andExperiments, which are not intended to limit the scope of the presentinvention.

EXAMPLES Example 1 Synthesis of Compound (I-7)

Step 1

Sodium carbonate (995 mg, 9.38 mmol) was dissolved in 30 ml of water andstarting material amino acid (1.0 g, 8.53 mmol) andN-carbethoxyphthalimide (2.49 g, 11.4 mmol) were added thereto. Themixture was stirred at room temperature overnight. The pH of the mixturewas adjusted to 1 by adding conc. hydrochloric acid. Precipitatedcrystals were washed with water and dried to give the desired compound(1.72 g, 82% yield).

¹H-NMR (CD₃OD) δ ppm: 1.59-1.77 (m, 4H), 2.34 (t, 2H, J=6.3 Hz), 3.69(t, 2H, J=6.6 Hz), 7.78-7.87 (m, 4H).

Step 2

The compound obtained in Step 1 (1.0 g, 4.0 mmol) was dissolved in 5 mlof dichloromethane at room temperature. Oxalyl chloride (0.459 ml, 5.2mmol) and trace amounts of DMF were added to the mixture underice-cooling and the mixture was reacted under ice-cooling and at roomtemperature, each for 30 min. After the solvent was removed underreduced pressure, 5 ml of dichloromethane was added. Under ice-cooling,4-butylaniline (664 mg, 4.4 mmol) and triethylamine (0.564 ml, 4.4 mmol)were added thereto and the mixture was reacted for 30 min. at roomtemperature. The reactant was poured into water and extracted withchloroform. The organic layer was washed with water and dried overmagnesium sulfate anhydride. The solvent was removed under reducedpressure and the residue was purified by silica gel chromatography togive the desired compound (1.49 g, 97% yield).

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.27-1.39 (m, 2H),1.51-1.62 (m, 2H), 1.72-1.84 (m, 4H), 2.40-2.46 (m, 2H), 2.56 (t, 2H,J=7.5 Hz), 3.76 (t, 1H, J=5.7 Hz), 7.12 (d, 2H, J=7.8 Hz), 7.33 (s, 1H),7.42 (d, 2H, J=8.1 Hz), 7.71-7.73 (m, 2H), 7.83-7.86 (m, 2H).

Step 3

After the compound obtained in Step 2 (1.49 g, 3.9 mmol) was dissolvedin 30 ml of ethanol, hydrazine monohydrate (0.591 mg, 11.8 mmol) wasadded and the mixture was reacted at 50° C. for 3 hours. The solvent wasremoved, 1 mol/l aqueous NaOH was added and the solution was extractedwith ethyl acetate. The organic layer was washed with water and driedover magnesium sulfate anhydride. The solvent was removed under reducedpressure to give the desired compound (808 mg, 83% yield).

¹H-NMR (CD₃OD) δ ppm: 0.93 (t, 3H, J=7.2 Hz), 1.28-1.40 (m, 2H),1.50-1.62 (m, 4H), 1.67-1.77 (m, 2H), 2.37 (t, 2H, J=7.5 Hz), 2.56 (t,2H, J=7.8 Hz), 2.68 (t, 2H, J=7.2 Hz), 7.11 (d, 2H, J=8.1 Hz), 7.42 (d,2H, J=8.4 Hz).

Step 4

The compound obtained in Step 3 (808 mg, 3.25 mmol) was suspended in 5ml of dichloromethane under ice-cooling and isopropylsulfonyl chloride(696 mg, 4.9 mmol) and triethylamine (494 mg, 4.9 mmol) were added.After the mixture was reacted under ice-cooling for an hour, thereactant was poured into water and extracted with chloroform. Theorganic layer was washed with water and dried over magnesium sulfateanhydride. The solvent was removed under reduced pressure and theresidue was purified by silica gel chromatography to give the desiredcompound quantitatively.

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.27-1.40 (m, 2H), 1.36(d, 6H, J=6.6 Hz), 1.51-1.69 (m, 4H), 1.77-1.86 (m, 2H), 2.38 (t, 2H,J=7.2 Hz), 2.56 (t, 2H, J=7.5 Hz), 3.12-3.21 (m, 3H), 4.38 (t, 1H, J=5.7Hz), 7.11 (d, 2H, J=8.4 Hz), 7.36-7.41 (m, 3H).

Example 2 Synthesis of Compound (I-10)

The desired compound was synthesized in a similar manner to Step 4 inExample 1 except that tert-butylsulfinyl chloride (689 mg, 4.9 mmol) andtriethylamine (494 mg, 4.9 mmol) were added to the compound obtained inStep 3 in Example 1.

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.22 (s, 9H), 1.30-1.37(m, 2H), 1.51-1.68 (m, 4H), 1.76-1.86 (m, 2H), 2.31-2.40 (m, 2H), 2.56(t, 2H, J=7.5 Hz), 3.15-3.26 (m, 3H), 7.11 (t, 2H, J=8.7 Hz), 7.42 (d,2H, J=8.1 Hz), 7.54 (s, 1H).

Example 3 Synthesis of Compound (I-11)

The compound obtained in Example 2 (352 mg, 1.0 mmol) was dissolved in 5ml of dichloromethane under ice-cooling and mCPBA (259 mg, 1.5 mmol) wasadded to the solution. The solution was reacted at room temperature foran hour and the insoluble material was filtered off. The filtrate waswashed with 1 mol/l NaOH, Na₂S₂O₅ and water, successively, and driedover magnesium sulfate anhydride. The solvent was removed under reducedpressure and the residue was purified by silica gel chromatography togive the desired compound (338 mg, 92% yield).

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.29-1.39 (m, 2H), 1.39(s, 9H), 1.51-1.68 (m, 4H), 1.76-1.84 (m, 2H), 2.37 (t, 2H, J=7.5 Hz),2.56 (t, 2H, J=7.8 Hz), 3.19-3.26 (m, 2H), 4.20 (t, 1H, J=5.7 Hz), 7.11(t, 2H, J=8.1 Hz), 7.42 (d, 2H, J=8.7 Hz), 7.46 (s, 1H).

Example 4 Synthesis of Compound (1-72)

Step 1

Starting material amino acid (a mixture of cis isomer and trans isomer)(1.0 g, 8.53 mmol) was dissolved in 7.5 ml of methanol. Thionyl chloride(1.0 ml, 13.7 mmol) was added to the mixture under ice-cooling and themixture was stirred at room temperature overnight. After the mixture wasconcentrated under reduced pressure, diethylether was added andprecipitated crystals were obtained by filtration. The crystals werewashed with diethylether and dried to give the desired compound (1.25 g,93% yield).

¹H-NMR (CDCl₃) δ ppm: 1.50-2.60 (m, 9H), 3.08-3.36 (m, 1H), 3.67 (s, 3H,CO₂Me of cis isomer), 3.71 (s, 3H, CO₂Me of trans isomer), 8.15-8.55 (m,3H).

Step 2

The desired sulfonamide (a mixture of cis isomer and trans isomer) wassynthesized from starting material methyl ester in similar manners toStep 3 in Example 1 and Example 2.

cis isomer

¹H-NMR (CDCl₃) δ ppm: 1.39 (s, 9H), 1.52-1.99 (m, 8H), 2.43-2.53 (m,1H), 3.42-3.55 (m, 1H), 3.69 (s, 3H), 3.85 (d, 1H, J=9.0 Hz).

Step 3

Starting material sulfonamide (19.4 g, 70.0 mmol, a mixture of cisisomer and trans isomer) was dissolved in 30 ml of methanol. To themixture, 28% sodium methoxide (284 ml, 140.0 mmol) was added andrefluxed with stirring under ice-cooling. After the solvent was removed,the residue was diluted with chloroform, and 1 mol/l HCl was added withstirring under ice-cooling until pH of an aqueous layer reached 3. Theaqueous layer was extracted with chloroform and the organic layer waswashed with water and dried over magnesium sulfate anhydride. Theobtained crude crystals were recrystallized from hexane-ethyl acetate togive the desired sulfonamide (trans isomer, 7.75 g, 40% yield).

trans isomer

¹H-NMR (CD₃OD) δ ppm: 1.16-1.32 (m, 2H), 1.39 (s, 9H), 1.44-1.52 (m,2H), 1.98-2.09 (m, 2H), 2.14-2.29 (m, 3H), 3.18-3.37 (m, 1H), 3.63 (d,1H, J=9.0 Hz), 3.67 (s, 3H).

Step 4

Starting material methyl ester (4.77 g, 17.2 mmol) was dissolved in 95ml of methanol and 1 mol/l NaOH (43 ml, 43.0 mmol) was added withstirring under ice-cooling. The mixture was stirred at room temperatureovernight and concentrated under reduced pressure. After 1 mol/l HCl wasadded with stirring until pH of the mixture reached 3 under ice-cooling,the precipitated crystals were collected by filtration, washed withwater and dried. The obtained crude crystals were recrystallized fromhexane-ethylacetate to give the desired carboxylic acid (4.20 g, 93%yield).

¹H-NMR (CDCl₃) δ ppm: 1.18-1.35 (m, 2H), 1.39 (s, 91), 1.46-1.63 (m,2H), 2.01-2.14 (m, 2H), 2.14-2.32 (m, 3H), 3.18-3.35 (m, 1H), 3.80 (d,1H, J=9.6 Hz).

Step 5

A starting material carboxylic acid (5.86 g, 22.3 mmol) was dissolved in88 ml of dichloromethane at room temperature. To the mixture, oxalylchloride (2.34 ml, 26.7 mmol) and catalytic amount of DMF were addedunder ice-cooling and stirred at room temperature for an hour. After thesolvent was removed under reduced pressure, dichloromethane (115 ml),substituted aniline (5.05 g, 24.5 mmol) and triethylamine (4.65 ml, 33.4mmol) were added. The mixture was stirred at room temperature for 2.5hours, the ice-cooling water was poured thereto, and the mixture wasextracted with chloroform. An organic layer was washed with water anddried over magnesium sulfate anhydride. The solvent was removed underreduced pressure and ethyl acetate and hexane were added to the residue.The precipitated crystals were collected with filtration to give thedesired amide (7.00 g, 70% yield).

¹H-NMR (CDCl₃) δ ppm: 1.25 (d, 6H, J=6.3 Hz), 1.17-1.42 (m, 2H), 1.40(s, 9H), 1.60-1.78 (m, 2H), 1.98-2.43 (m, 7H), 3.20-3.43 (m, 3H), 3.67(d, 1H, J=9.6 Hz), 3.74-3.86 (m, 2H), 6.86 (d, 2H, J=9.0 Hz), 7.04 (s,1H), 7.38 (d, 2H, J=9.0 Hz).

Example 5 Synthesis of Compound (I-2)

Step 1

After starting material diamine (461 mg, 2.5 mmol) was suspended indichloromethane under ice-cooling, an acid chloride (500 mg, 2.5 mmol)and triethylamine (773 mg, 7.5 mmol) were added and the mixture wasreacted for 30 min. Water and dichloromethane were added to the reactantand insoluble materials were filtered off. The organic layer was washedwith water and dried over magnesium sulfate anhydride. The solvent wasremoved under reduced pressure to give the desired compound as a residue(100 mg, 15% yield).

¹H-NMR (CDCl₃) δ ppm: 0.93 (t, 3H, J=7.2 Hz), 1.30-1.42 (m, 2H),1.57-1.67 (m, 2H), 2.66 (t, 2H, J=7.8 Hz), 3.50 (brs, 1H), 6.57 (s, 1H),6.68 (d, 2H, J=8.7 Hz), 7.26 (d, 2H, J=8.4 Hz), 7.39 (d, 2H, J=8.7 Hz),7.68 (s, 1H), 7.75 (d, 2H, J=8.1 Hz).

Step 2

The desired compound was synthesized in a similar manner to Step 4 inExample 1.

¹H-NMR (CDCl₃) δ ppm: 0.94 (t, 3H, J=7.5 Hz), 1.34-1.44 (m, 2H), 1.40(d, 6H, J=6.6 Hz), 1.59-1.68 (m, 2H), 2.69 (t, 2H, J=7.8 Hz), 3.24-3.35(m, 1H), 6.49 (s, 1H), 7.23-7.32 (m, 4H), 7.6 (d, 2H, J=8.7 Hz), 7.79(d, 2H, J=8.1 Hz), 7.85 (s, 1H).

Example 6 Synthesis of Compound (I-31)

Step 1

A starting material diamine (8.37 g, 73.3 mmol) was dissolved in 30 mlof dioxane at room temperature and a solution of Boc₂O (2 g, 9.2 mmol)in dioxane (30 ml) was added. The mixture was reacted at roomtemperature for 3 days and the solvent was removed. Water was added tothe residue and the mixture was extracted with chloroform. The organiclayer was washed with water and dried over magnesium sulfate anhydride.The solvent was removed under reduced pressure to give the desiredcompound as a residue (1.8 g, 92% yield based on Boc₂O).

¹H-NMR (CDCl₃) δ ppm: 1.07-1.26 (m, 6H), 1.44 (s, 9H), 1.84-2.00 (m,4H), 2.58-2.67 (m, 1H), 3.37 (brs, 1H), 4.43 (brs, 1H).

Step 2

The desired compound was synthesized in a similar manner to Step 1 inExample 5.

¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=7.2 Hz), 1.26-1.42 (m, 6H), 1.45(s, 9H), 1.54-1.68 (m, 2H), 1.99-2.12 (m, 4H), 2.64 (t, 2H, J=7.8 Hz),3.43 (brs, 1H), 3.90-4.00 (m, 1H), 4.48 (d, 1H, J=5.7 Hz), 5.95 (d, 1H,J=8.4 Hz), 7.21 (d, 2H, J=8.4 Hz), 7.65 (d, 2H, J=8.4 Hz).

Step 3

A starting material Boc compound (2.08 g, 5.55 mmol) was dissolved in 20ml of ethyl acetate under ice-cooling and 20 ml of 4mol/l HCl/AcOEt wasadded. The mixture was reacted at room temperature for an hour and thesolvent was removed under reduced pressure to give the desired compoundas a residue (1.7 g, 98% yield).

¹H-NMR (CD₃OD) δ ppm: 0.93 (t, 3H, J=7.2 Hz), 1.29-1.41 (m, 2H),1.50-1.66 (m, 6H), 2.02-2.18 (m, 4H), 2.66 (t, 2H, J=7.8 Hz), 3.13 (brs,1H), 3.82-3.94 (m, 1H), 7.26 (d, 2H, J=8.7 Hz), 7.72 (d, 2H, J=8.4 Hz).

Step 4

The desired compound was synthesized in a similar manner to Step 4 inExample 1.

¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=7.5 Hz), 1.21 (s, 9H), 1.28-1.62(m, 8H), 2.07-2.14 (m, 4H), 2.64 (t, 2H, J=7.8 Hz), 3.11 (d, 1H, J=5.1Hz), 3.20 (brs, 1H), 3.90-4.04 (m, 1H), 6.06-6.14 (m, 1H), 7.21 (t, 2H,J=8.1 Hz), 7.67 (t, 2H, J=8.4 Hz).

Example 7 Synthesis of Compound (1-32)

The desired compound was synthesized from the compound obtained inExample 6 in a similar manner to Example 3.

¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=7.2 Hz), 1.27-1.65 (m, 8H), 1.40(s, 9H), 2.10-2.23 (m, 4H), 2.65 (t, 2H, J=7.5 Hz), 3.23-3.35 (m, 1H),3.49 (s, 1H), 3.88-4.02 (m, 1H), 5.84-5.92 (m, 1H), 7.13 (t, 2H, J=8.4Hz), 7.65 (d, 2H, J=8.1 Hz).

Example 8 Synthesis of Compound (1-5)

Step 1

The desired compound was synthesized in a similar manner to Step 2 inExample 1.

¹H-NMR (CDCl₃) δ ppm: 0.94 (t, 3H, J=7.5 Hz), 1.30-1.42 (m, 2H),1.50-1.65 (m, 2H), 2.61 (t, 2H, J=7.8 Hz), 7.20 (d, 2H, J=7.2 Hz),7.48-7.51 (m, 3H), 7.72 (s, 1H), 7.88-7.90 (m, 1H).

Step 2

To a mixture of a starting material nitro compound (593 mg, 1.95 mmol)and tin (358 mg, 3.0 mmol), 30 ml of 6 mol/l HCl and 6 ml of THF wereadded and reacted at 50° C. for 3 hours. After cooling, the solvent wasremoved and the residue was neutralized 10% with NaOH and extracted withchloroform. The organic layer was washed with water and dried overmagnesium sulfate anhydride. The solvent was removed under reducedpressure and the residue was purified by silica gel chromatography togive the desired compound (110 mg, 21% yield).

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.26-1.39 (m, 2H),1.49-1.59 (m, 2H), 2.50 (t, 2H, J=7.8 Hz), 4.37 (s, 1H), 6.65 (d, 2H,J=8.4 Hz), 6.97 (d, 2H, J=8.4 Hz), 7.14 (d, 1H, J=8.4 Hz), 7.43 (d, 1H,J=8.7 Hz).

Step 3

The desired compound was synthesized in a similar manner to Step 4 inExample 1.

¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=7.2 Hz), 1.28-1.41 (m, 2H), 1.46(d, 6H, J=6.9 Hz), 1.53-1.63 (m, 2H), 2.59 (t, 2H, J=7.8 Hz), 3.35-3.44(m, 1H), 7.15 (d, 2H, J=8.7 Hz), 7.38 (s, 1H), 7.45 (d, 2H, J=8.7 Hz),7.57 (s, 1H).

Example 9 Synthesis of Compound (1-4)

Step 1

The desired compound was synthesized in a similar manner to Step 4 inExample 1.

¹H-NMR (CDCl₃) δ ppm: 1.44 (d, 6H, J=6.9 Hz), 3.33-3.43 (m, 1H), 3.88(s, 9H), 6.24-6.26 (m, 1H), 7.11-7.14 (m, 2H).

Step 2

The desired compound was synthesized in a similar manner to Step 4 inExample 4. ¹H -NMR (CDCl₃) δ ppm: 1.44 (d, 6H, J=6.3 Hz), 3.33-3.45 (m,1H), 6.25-6.28 (m, 1H), 7.27-7.28 (m, 1H), 7.51 (s, 1H).

Step 3

The desired compound was synthesized in a similar manner to Step 2 inExample 1.

¹H-NMR (CD₃OD) δ ppm: 0.92 (t, 3H, J=6.9 Hz), 1.28-1.41 (m, 2H), 1.46(d, 6H, J=6.3 Hz), 1.53-1.63 (m, 2H), 2.58 (t, 2H, J=7.8 Hz), 3.33-3.43(m, 1H), 6.27-6.29 (m, 1H), 7.14-7.16 (m, 3H), 7.50 (d, 2H, J=8.4 Hz),7.90 (s, 1H).

Example 10 Synthesis of Compound (I-28)

Step 1

The desired compound was synthesized in a similar manner to Step 1 inExample 1.

¹H-NMR (CDCl₃) δ ppm: 1.37-1.52 (m, 3H), 1.74-1.79 (m, 2H), 2.07-2.13(m, 2H), 2.28-2.42 (m, 2H), 3.72-3.81 (m, 1H), 4.09-4.20 (m, 1H),7.68-7.73 (m, 2H), 7.81-7.85 (m, 2H).

Step 2

4-butylphenyl isocyanate (2.85 g, 16.3 mmol) was dissolved in 30 ml ofTHF, and a starting material alcohol (1.0 g, 4.08 mmol) andbis(tributyltin)oxide (972 mg, 1.63 mmol) were added. After the mixturewas stirred overnight, the solvent was removed, water was added and thesolution was extracted with chloroform. The organic layer was washedwith water and dried over magnesium sulfate anhydride. The solvent wasremoved under reduced pressure and the residue was purified by silicagel chromatography to give the desired compound (332 mg, 19% yield).

¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=6.9 Hz), 1.30-1.40 (m, 2H),1.48-1.62 (m, 4H), 1.79-1.83 (m, 2H), 2.21-2.25 (m, 2H), 2.37-2.50 (m,2H), 2.57 (t, 2H, J=7.8 Hz), 4.11-4.22 (m, 1H), 4.77-4.87 (m, 1H), 6.49(s, 1H), 7.11 (d, 2H, J=8.7 Hz), 7.28 (d, 2H, J=8.7 Hz), 7.69-7.73 (m,2H), 7.80-7.84 (m, 2H).

Step 3

The desired compound was synthesized in similar manners to Step 3 inExample 1 and Example 2.

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.21 (s, 9H), 1.30-1.62(m, 8H), 2.08 (d, 4H, J=11.1 Hz), 2.56 (t, 2H, J=7.8 Hz), 3.04 (d, 1H,J=4.8 Hz), 3.20-3.30 (m, 1H), 4.65-4.76 (m, 1H), 6.57 (s, 1H), 7.10 (d,2H, J=8.7 Hz), 7.26 (d, 2H, J=8.1 Hz).

Example 11 Synthesis of Compound (I-29)

The desired compound was synthesized in a similar manner to Example 3.

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.23-1.62 (m, 8H), 1.40(s, 9H), 2.12 (d, 4H, J=14.4 Hz), 2.56 (t, 2H, J=7.8 Hz), 3.28-3.40 (m,1H), 3.90 (s, 1H), 4.60-4.73 (m, 1H), 6.57 (s, 1H), 7.10 (d, 2H, J=8.4Hz), 7.25 (d, 2H, J=8.4 Hz).

Example 12 Synthesis of Compound (I-114)

Lawesson's reagent[2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide](132 mg) was added to a solution of 100 mg of Compound (I-110)synthesized in a similar manner to Example 1 in toluene (2.7 ml) and themixture was stirred at 80° C. for 3 hours. The reactant was concentratedunder reduced pressure and the residue was purified by silica gelchromatography (ethyl acetate:n-hexane=1:1) to give pale yellow crystals(82.3 mg, 79%). The crystals were recrystallized from methylenechloride-diisopropyl ether to give the desired compound as colorlessneedles (50.5 mg, 48%).

Example 13 Synthesis of Compound (1-120)

Step 1

Ethyl 4-amino-1-piperidinecarboxylate (300 mg) and triethylamine (258mg) were dissolved in 5 ml of dichloromethane. To the mixture, 2 ml ofsolution of t-butylsulfinyl chloride (222 mg) in dichloromethane wasadded and the mixture was stirred at room temperature for 4 hours. Thesolution was partitioned into an aqueous solution of potassium hydrogensulfate and ethyl acetate. The organic layer was washed with brine anddried over magnesium sulfate anhydride. The solvent was removed underreduced pressure and the residue was purified by silica gelchromatography to give 378 mg of 4-t-butylsulfiny amino-1-ethoxycarbonylpiperidine.

Step 2

In a mixture of 5 ml of 2-propanol and 5 ml of water, 378 mg of4-t-butylsulfinylamino-1-ethoxycarbonyl piperidine was suspended and1.77 g of barium hydroxide was added. The mixture was refluxed withstirring and heating for 4 hours. The mixture was diluted with methanoland the insoluble material was filtered off. The solvent was removedunder reduced pressure to give 4-t-butylsulfinylaminopiperidine. Withoutpurification, the obtained material was dissolved in 5 ml of THF, and984 mg of N-phenoxycarbonyl-4-butyl aniline and 236 mg of diisopropylethylamine were added, followed by stirring at room temperatureovernight. An aqueous solution of potassium hydrogen sulfate was addedto the mixture and the mixture was extracted with ethyl acetate. Theorganic layer was washed with brine and dried over magnesium sulfateanhydride. The solvent was removed under reduced pressure and theresidue was purified by silica gel chromatography to give 291 mg of4-t-butylsulfinylaminopiperidine-1-carboxlic acid(4-t-butylphenyl)amide.

¹H-NMR (CDCl₃) δ ppm: 0.89 (t, 3H, J=7.3 Hz), 1.19 (s, 9H), 1.25-1.38(m, 4H), 1.40-1.60 (m, 4H), 1.89-2.03 (m, 3H), 2.52 (t, 2H, J=7.7 Hz),2.89-3.04 (m, 2H), 3.14 (d, 1H, J=5.2 Hz), 3.37 (m, 1H), 3.96 (m, 2H),6.67 (s, 1H), 7.05 (d, 2H, J=8.5 Hz), 7.22 (d, 2H, J=8.5 Hz).

Step 3

In a mixture of 2 ml of methanol and 2 ml of methylene chloride, 291 mgof 4-t-butylsulfinyl aminopiperidine-1-carboxlicacid(4-t-butylphenyl)amide was dissolved. To the mixture, 570 mg of80%-MMPP (magnesium monoperoxyphthalate hexahydrate) was added and themixture was stirred at room temperature for 2 hours. The solution wasdiluted with water and extracted with ethyl acetate. The organic layerwas washed with brine and dried over magnesium sulfate anhydride. Thesolvent was removed under reduced pressure and the residue was purifiedby silica gel chromatography to give 130 mg of4-t-butylsulfonylaminopiperidine-1-carboxylic acid(4-butylphenyl)amide(I-120).

Other Compounds (I) are synthesized by the similar methods. Thestructures and physical properties are shown below.

I-2

¹H-NMR (CDCl₃) δ ppm: 0.94 (t, 3H, J=7.5 Hz), 1.34-1.44 (m, 2H), 1.40(d, 6H, J=6.6 Hz), 1.59-1.68 (m, 2H), 2.69 (t, 2H, J=7.8 Hz), 3.24-3.35(m, 1H), 6.49 (s, 1H), 7.23-7.32 (m, 4H), 7.6 (d, 2H, J=8.7 Hz), 7.79(d, 2H, J=8.1 Hz), 7.85 (s, 1H).

I-3

¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=7.2 Hz), 1.30-1.39 (m, 2H), 1.37(d, 6H, J=6.9 Hz), 1.57 (quint, 2H, J=7.5 Hz), 1.96 (quint, 2H, J=6.6Hz), 2.49 (t, 2H, J=6.6 Hz), 2.57 (t, 2H, J=7.8 Hz), 3.16-3.26 (m, 3H),4.62 (brs, 1H), 7.12 (d, 2H, J=8.1 Hz), 7.43 (d, 2H, J=8.4 Hz), 7.64 (s,1H).

I-4

¹H-NMR (CD₃OD) δ ppm: 0.92 (t, 3H, J=6.9 Hz), 1.28-1.41 (m, 2H), 1.46(d, 6H), J=6.3 Hz), 1.53-1.63 (m, 2H), 2.58 (t, 2H), J=7.8 Hz),3.33-3.43 (m, 1H), 6.27-6.29 (m, 1H), 7.14-7.16 (m, 3H), 7.50 (d, 2H,J=8.4 Hz), 7.90 (s, 1H).

I-5

¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=7.2 Hz), 1.28-1.41 (m, 2H), 1.46(d, 6H, J=6.9 Hz), 1.53-1.63 (m, 2H), 2.59 (t, 2H, J=7.8 Hz), 3.35-3.44(m, 1H), 7.15 (d, 2H, J=8.7 Hz), 7.38 (s, 1H), 7.45 (d, 2H, J=8.7 Hz),7.57 (s, 1H).

I-6

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.29-1.39 (m, 2H), 1.37(d, 6H, J=6.9 Hz), 1.55 (quint, 2H, J=7.5 Hz), 2.55 (t, 2H, J=5.1 Hz),3.18-3.27 (m, 1H), 3.92 (d, 2H, J=6.0 Hz), 5.51 (t, 1H, J=5.7 Hz), 7.10(d, 2H, J=8.4 Hz), 7.39 (d, 2H, J=8.4 Hz), 8.23 (s, 1H).

I-7

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.28-1.38 (m, 2H), 1.37(d, 6H, J=6.9 Hz), 1.51-1.67 (m, 4H), 1.78-1.88 (m, 2H), 2.39 (t, 2H,J=7.2 Hz), 2.57 (t, 2H, J=7.5 Hz), 3.12-3.22 (m, 3H), 4.30-4.37 (m, 1H),7.12 (d, 2H, J=8.4 Hz), 7.36-7.42 (m, 3H).

I-8

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.21-1.47 (m, 4H), 1.35(d, 6H, J=6.6 Hz), 1.51-1.63 (m, 4H), 1.67-1.77 (m, 2H), 2.34 (t, 2H,J=7.5 Hz), 2.55 (t, 2H, J=7.8 Hz), 3.08-3.17 (m, 3H), 4.71 (t, 1H, J=6.0Hz), 7.09 (d, 2H, J=8.1 Hz), 7.43 (d, 2H, J=8.4 Hz), 7.74 (s, 1H).

I-9

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.29-1.39 (m, 2H), 1.35(d, 6H, J=6.9 Hz), 1.50-1.60 (m, 2H), 2.54 (t, 2H, J=7.8 Hz), 2.64 (t,2H, J=5.7 Hz), 3.14-3.23 (m, 1H), 3.41-3.47 (m, 2H), 5.29 (t, 1H, J=6.3Hz), 7.10 (d, 2H, J=8.4 Hz), 7.39 (d, 2H, J=8.4 Hz), 7.91 (s, 1H).

I-10

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.22 (s, 9H), 1.30-1.37(m, 2H), 1.51-1.68 (m, 4H), 1.76-1.86 (m, 2H), 2.31-2.40 (m, 2H), 2.56(t, 2H, J=7.5 Hz), 3.15-3.26 (m, 3H), 7.11 (t, 2H, J=8.7 Hz), 7.42 (d,2H, J=8.1 Hz), 7.54 (s, 1H).

I-11

mp: 128-129° C. ¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.29-1.39(m, 2H), 1.39 (s, 9H), 1.51-1.68 (m, 4H), 1.76-1.84 (m, 2H), 2.37 (t,2H, J=7.5 Hz), 2.56 (t, 2H, J=7.8 Hz), 3.19-3.26 (m, 2H), 4.20 (t, 1H,J=5.7 Hz), 7.11 (d, 2H, J=8.1 Hz), 7.42 (d, 2H, J=8.7 Hz), 7.46 (s, 1H).

I-12

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.28-1.37 (m, 2H),1.47-1.68 (m, 6H), 2.23 (t, 2H, J=7.2 Hz), 2.56 (t, 2H, J=7.5 Hz),2.90-2.97 (m, 2H), 5.10 (brs, 1H), 7.11 (d, 2H, J=8.4 Hz), 7.36 (d, 2H,J=8.1 Hz), 7.50-7.68 (m, 3H), 7.93 (d, 1H, J=8.1 Hz), 8.06 (d, 1H, J=8.4Hz), 8.24 (d, 1H, J=7.5 Hz), 8.66 (d, 1H, J=8.7 Hz).

I-13

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.28-1.40 (m, 2H),1.45-1.73 (m, 6H), 2.23 (t, 2H, J=7.5 Hz), 2.56 (t, 2H, J=7.8 Hz), 2.88(s, 6H), 2.88-2.95 (m, 2H), 5.04 (brs, 1H), 7.10 (d, 2H, J=8.1 Hz), 7.17(d, 1H, J=7.2 Hz), 7.37 (d, 2H, J=8.4 Hz), 7.48-7.54 (m, 2H), 8.23 (d,1H, J=7.2 Hz), 8.30 (d, 1H, J=8.7 Hz), 8.53 (d, 1H, J=8.4 Hz).

I-14

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.30-1.43 (m, 6H), 1.36(d, 6H, J=6.6 Hz), 1.51-1.62 (m, 4H), 1.67-1.78 (m, 2H), 2.34 (t, 2H,J=7.5 Hz), 2.56 (t, 2H, J=7.8 Hz), 3.09-3.20 (m, 3H), 4.34 (brs, 1H),7.10 (d, 2H, J=8.4 Hz), 7.41-7.44 (m, 3H).

I-15

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.23 (s, 9H), 1.27-1.80(m, 12H), 2.30-2.38 (m, 2H), 2.56 (t, 2H, J=7.5 Hz), 3.15 (brs, 2H),7.11 (d, 2H, J=7.8 Hz), 7.43 (d, 2H, J=7.8 Hz), 7.59 (s, 1H).

I-16

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.29-1.44 (m, 6H), 1.39(s, 9H), 1.51-1.61 (m, 4H), 1.68-1.78 (m, 2H), 2.35 (t, 2H, J=7.5 Hz),2.56 (t, 2H, J=8.1 Hz), 3.15-3.21 (m, 2H), 4.14-4.23 (m, 1H), 7.11 (d,2H, J=7.8 Hz), 7.36-7.44 (m, 3H).

I-19

¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=7.5 Hz), 1.21 (s, 9H), 1.30-1.40(m, 2H), 1.55-1.72 (m, 6H), 2.64 (t, 2H, J=7.8 Hz), 3.08-3.33 (m, 3H),3.42-3.50 (m, 2H), 6.39 (s, 1H), 7.22 (d, 2H, J=8.4 Hz), 7.69 (d, 2H,J=8.1 Hz).

I-20

¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=7.2 Hz), 1.31-1.39 (m, 2H), 1.39(s, 9H), 1.55-1.72 (m, 6H), 2.64 (t, 2H, J=7.8 Hz), 3.24 (quart, 2H,J=6.6 Hz), 3.48 (quart, 2H, J=6.6 Hz), 4.21 (t, 1H, J=6.3 Hz), 6.29 (s,1H), 7.22 (d, 2H, J=7.8 Hz), 7.67 (d, 2H, J=8.1 Hz).

I-21

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.23 (s, 9H), 1.30-1.42(m, 2H), 1.50-2.02 (m, 10H), 2.30-2.42 (m, 1H), 2.57 (t, 2H, J=8.1 Hz),3.10 (brs, 1H), 3.57 (brs, 1H), 7.12 (d, 2H, J=8.4 Hz), 7.41 (d, 2H,J=7.8 Hz).

I-22

mp: 78-79° C. ¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.30-1.40(m, 2H), 1.40 (s, 9H), 1.50-1.65 (m, 4H), 1.70-1.98 (m, 8H), 2.30-2.40(m, 1H), 2.57 (t, 2H, J=7.5 Hz), 3.58-3.70 (m, 1H), 4.16 (d, 1H, J=9.3Hz), 7.11-7.15 (m, 3H), 7.40 (d, 2H, J=8.1 Hz).

I-23

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.21 (s, 9H), 1.21-1.41(m, 4H), 1.51-1.64 (m, 4H), 1.86-2.01 (m, 4H), 2.12-2.25 (m, 1H), 2.56(t, 2H, J=7.5 Hz), 2.87-2.96 (m, 1H), 3.00-3.12 (m, 1H), 3.23-3.34 (m,1H), 3.67-3.75 (m, 1H), 7.11 (d, 2H, J=8.1 Hz), 7.40 (d, 2H, J=8.4 Hz).

I-24

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.25-1.37 (m, 2H), 1.40(s, 9H, 1.48-1.65 (m, 6H), 1.90 (d, 2H, J=11.7 Hz), 2.02 (d, 2H, J=11.7Hz), 2.12-2.24 (m, 1H), 2.56 (t, 2H, J=7.5 Hz), 3.04 (t, 2H, J=6.3 Hz),4.31 (t, 1H, J=5.7 Hz), 7.11 (d, 2H, J=8.1 Hz), 7.42 (d, 2H, J=8.4 Hz).

I-25

mp: 232-233° C. ¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.23-1.40(m, 4H), 1.40 (s, 9H), 1.51-1.76 (m, 4H), 2.01-2.26 (m, 5H), 2.56 (t,2H, J=7.5 Hz), 3.22-3.38 (m, 1H), 3.79 (d, 1H, J=9.3 Hz), 7.11 (d, 2H,J=8.7 Hz), 7.17 (s, 1H), 7.40 (d, 2H, J=8.4 Hz).

I-26

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.22 (s, 9H), 1.28-1.40(m, 2H), 1.52-1.62 (m, 2H), 1.85-1.96 (m, 1H), 2.00-2.14 (m, 1H),2.38-2.53 (m, 2H), 2.56 (t, 2H, J=7.5 Hz), 3.22-3.37 (m, 3H), 7.11 (d,2H, J=8.4 Hz), 7.45 (d, 2H, J=8.4 Hz), 8.19 (s, 1H).

I-27

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.30-1.40 (m, 2H), 1.40(s, 9H), 1.52-1.61 (m, 2H), 1.95 (quint, 2H, J=6.3 Hz), 2.50 (t, 2H,J=6.9 Hz), 2.56 (t, 2H, J=7.8 Hz), 3.31 (quart, 2H, J=6.0 Hz), 4.30-4.36(m, 1H), 7.12 (d, 2H, J=8.4 Hz), 7.43 (d, 2H, J=8.4 Hz), 7.65 (s, 1H).

I-28

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.21 (s, 9H), 1.30-1.62(m, 8H), 2.08 (d, 4H, J=11.1 Hz), 2.56 (t, 2H, J=7.8 Hz), 3.04 (d, 1H,J=4.8 Hz), 3.20-3.30 (m, 1H), 4.65-4.76 (m, 1H), 6.57 (s, 1H), 7.10 (d,2H, J=8.7 Hz), 7.26 (d, 2H, J=8.1 Hz).

I-29

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.2 Hz), 1.23-1.62 (m, 8H), 1.40(s, 9H), 2.12 (d, 4H, J=14.4 Hz), 2.56 (t, 2H, J=7.8 Hz), 3.28-3.40 (m,1H), 3.90 (s, 1H), 4.60-4.73 (m, 1H), 6.57 (s, 1H), 7.10 (d, 2H, J=8.4Hz), 7.25 (d, 2H, J=8.4 Hz).

I-30

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.26-1.39 (m, 2H),1.51-1.64 (m, 4H), 1.72-1.81 (m, 2H), 2.34 (t, 2H, J=6.9 Hz), 2.56 (t,2H, J=7.8 Hz), 2.95-3.01 (m, 2H), 4.84 (t, 1H, J=5.7 Hz), 6.99-7.12 (m,6H), 7.19-7.24 (m, 1H), 7.30 (s, 1H), 7.38-7.43 (m, 4H), 7.79 (d, 2H,J=8.7 Hz).

I-31

¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=7.5 Hz), 1.21 (s, 9H), 1.28-1.62(m, 8H), 2.07-2.14 (m, 4H), 2.64 (t, 2H, J=7.8 Hz), 3.11 (d, 1H, J=5.1Hz), 3.20 (brs, 1H), 3.90-4.04 (m, 1H), 6.06-6.14 (m, 1H), 7.21 (t, 2H,J=8.1 Hz), 7.67 (t, 2H, J=8.4 Hz).

I-32

¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=7.2 Hz), 1.27-1.65 (m, 8H), 1.40(s, 9H), 2.10-2.23 (m, 4H), 2.65 (t, 2H, J=7.5 Hz), 3.23-3.35 (m, 1H),3.49 (s, 1H), 3.88-4.02 (m, 1H), 5.84-5.92 (m, 1H), 7.13 (t, 2H, J=8.4Hz), 7.65 (d, 2H, J=8.1 Hz).

I-33

¹H-NMR (CDCl₃) δ ppm: 0.94 (t, 3H, J=7.2 Hz), 1.30-1.42 (m, 2H), 1.32(s, 9H), 1.57-1.66 (m, 2H), 2.67 (t, 2H, J=7.8 Hz), 5.61 (s, 1H), 6.93(d, 2H, J=8.7 Hz), 7.25 (d, 2H, J=8.4 Hz), 7.49 (d, 2H, J=9.0 Hz), 7.80(d, 2H, J=8.1 Hz), 8.22 (s, 1H).

I-34

¹H-NMR (CD₃OD) δ ppm: 0.95 (t, 3H, J=7.5 Hz), 1.35 (s, 9H), 1.35-1.44(m, 2H), 1.57-1.69 (m, 2H), 2.69 (t, 2H, J=7.5 Hz), 7.28-7.33 (m, 4H),7.56 (d, 2H, J=9.0 Hz), 7.83 (d, 2H, J=8.4 Hz).

I-36

¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=7.5 Hz), 1.31-1.70 (m, 11H), 1.39(s, 9H), 1.75-1.85 (m, 1H), 2.65 (t, 2H, J=8.1 Hz), 3.13 (t, 2H, J=6.6Hz), 3.40 (t, 2H, J=7.2 Hz), 4.10 (t, 1H, J=5.7 Hz), 6.21 (t, 1H, J=5.7Hz), 7.23 (d, 2H, J=8.1 Hz), 7.67 (d, 2H, J=8.4 Hz).

I-37

¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=7.5 Hz), 0.95-1.10 (m, 2H),1.31-1.40 (m, 2H), 1.39 (s, 9H), 1.55-1.63 (m, 4H), 1.80-1.92 (m, 4H),2.65 (t, 2H, J=7.8 Hz), 3.03 (t, 2H, J=6.6 Hz), 3.31 (t, 2H, J=6.6 Hz),4.06 (t, 1H, J=6.0 Hz), 6.22 (t, 1H, J=6.0 Hz), 7.23 (d, 2H, J=8.4 Hz),7.67 (d, 2H, J=8.1 Hz).

I-39

¹H-NMR (CDCl₃) δ ppm: 1.13 (t, 3H, J=7.2 Hz), 1.39 (s, 9H), 1.69-1.97(m, 8H), 2.27-2.38 (m, 1H), 3.29-3.35 (m, 4H), 3.60-3.70 (m, 1H), 4.52(d, 1H, J=9.3 Hz), 6.64 (d, 2H, J=8.4 Hz), 7.22 (s, 1H), 7.31 (d, 2H,J=9.0 Hz).

I-40

¹H-NMR (CDCl₃) δ ppm: 1.38 (s, 9H), 1.68-1.96 (m, 8H), 2.30-2.40 (m,1H), 3.11 (t, 4H, J=4.8 Hz), 3.60-3.72 (m, 1H), 3.86 (t, 4H, J=4.8 Hz),4.51 (brs, 1H), 6.89 (d, 2H, J=9.0 Hz), 7.42 (d, 2H, J=8.7 Hz).

I-41

mp:>278° C. (dec.); ¹H-NMR (CDCl₃) δ ppm: 1.18-1.40 (m, 2H), 1.40 (s,9H), 1.62-1.75 (m, 2H), 2.01-2.27 (m, 5H), 3.10-3.13 (m, 4H), 3.22-3.38(m, 1H), 3.72 (d, 1H, J=9.3 Hz), 3.85-3.88 (m, 4H), 6.87 (d, 2H, J=9.0Hz), 7.10 (s, 1H), 7.40 (d, 2H, J=9.0 Hz).

I-42

¹H-NHR (CDCl₃) δ ppm: 1.40 (s, 9H), 1.61-1.97 (m, 8H), 2.16 (s, 3H),2.33-2.43 (m, 1H), 3.60-3.70 (m, 1H), 4.66 (brs, 1H), 7.12 (d, 1H, J=8.7Hz), 7.46-7.50 (m, 1H), 7.62 (s, H), 7.75-7.78 (m, 1H), 7.86-7.91 (m,2H).

I-43

¹H-NMR (CDCl₃) δ ppm: 1.40 (s, 9H), 1.62-2.00 (m, 8H), 1.87 (s, 3H),2.36-2.47 (m, 1H), 3.24 (s, 3H), 3.64-3.74 (m, 1H), 4.87 (brs, 1H), 7.13(d, 2H, J=9.0 Hz), 7.64 (d, 2H, J=8.4 Hz), 7.81 (s, H).

I-44

mp: 235-236° C. ¹H-NMR (CDCl₃) δ ppm: 1.13 (t, 6H, J=6.9 Hz), 1.18-1.33(m, 2H), 1.40 (s, 9H), 1.60-1.77 (m, 2H), 2.00-2.26 (m, 5H), 3.28-3.35(m, 4H), 3.73 (d, 1H, J=9.3 Hz), 6.60-6.70 (m, 2H), 7.03 (brs, 1H), 7.31(d, 2H, J=7.8 Hz).

I-45

mp:>268° C. (dec.); ¹H-NMR (CDCl₃) δ ppm: 1.20-1.34 (m, 2H), 1.40 (s,9H), 1.56-1.76 (m, 8H), 2.00-2.26 (m, 5H), 3.06-3.14 (m, 4H), 3.24-3.36(m, 1H), 3.72 (d, 1H, J=9.3 Hz), 6.90 (d, 2H, J=8.7 Hz), 7.09 (s, 1H),7.36 (d, 2H, J=8.7 Hz).

I-46

mp:>272° C. (dec.); ¹H-NMR (DMSO-d₆) δ ppm: 1.28 (s, 9H), 1.31-1.59 (m,7H), 1.87-2.00 (m, 4H), 2.23-2.34 (m, 1H), 3.00-3.16 (m, 1H), 4.35-4.45(m, 2H), 6.81 (d, 1H, J=9.0 Hz), 7.16 (t, 1H, J=7.2 Hz), 7.43 (t, 1H,J=8.4 Hz), 7.52-7.58 (m, 3H), 8.04 (d, 1H, J=7.8 Hz), 8.43 (s, 1H).

I-47

¹H-NMR (CDCl₃) δ ppm: 1.20-1.36 (m, 2H), 1.40 (s, 9H), 1.62-1.77 (m,2H), 1.98-2.32 (m, 5H), 3.31-3.40 (m, 1H), 3.62 (d, 1H, J=9.0 Hz), 7.08(s, 1H), 7.29 (d, 2H, J=9.0 Hz), 7.61 (d, 2H, J=9.0 Hz).

I-48

¹H-NMR (CDCl₃) δ ppm: 1.22-1.36 (m, 2H), 1.40 (s, 9H), 1.62-1.77 (m,2H), 2.00-2.31 (m, 5H), 3.24-3.40 (m, 1H), 3.62 (d, 1H, J=10.2 Hz), 7.01(t, 2H, J=8.7 Hz), 7.09 (s, 1H), 7.42-7.50 (m, 2H).

I-49

mp: 270° C. (dec.);

¹H-NMR (CDCl₃) δ ppm: 1.20-1.36 (m, 2H), 1.40 (s, 9H), 1.61-1.77 (m,2H), 1.95-2.30 (m, 9H), 3.17-3.38 (m, 5H), 3.67 (d, 1H, J=9.3 Hz), 6.50(d, 2H, J=9.0 Hz), 6.97 (s, 1H), 7.30 (d, 2H, J=9.0 Hz).

I-50

mp: 252-253° C. ¹H-NMR (CDCl₃) δ ppm: 1.21-1.37 (m, 2H), 1.40 (s, 9H),1.62-1.78 (m, 2H), 1.98-2.32 (m, 5H), 3.26-3.40 (m, 1H), 3.68 (d, 1H,J=9.6 Hz), 6.94-7.02 (m, 4H), 7.08 (t, 1H, J=7.5 Hz), 7.13 (s, 1H), 7.31(t, 2H, J=7.5 Hz), 7.46 (d, 2H, J=9.0 Hz).

I-51

mp: 278-279° C. ¹H-NMR (CDCl₃) δ ppm: 1.02 (d, 6H, J=6.9 Hz), 1.35 (s,9H), 1.39-1.71 (m, 6H), 1.90-2.09 (m, 2H), 3.16-3.30 (m, 1H), 3.46 (d,1H, J=9.0 Hz), 4.92-5.01 (m, 1H), 6.91-6.95 (m, 2H), 7.00-7.07 (m, 3H),7.13-7.16 (m, 2H), 7.30-7.36 (m, 2H).

I-52

mp: 276-277° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.36 (m, 2H), 1.40 (s, 9H),1.60-1.78 (m, 2H), 1.98-2.30 (m, 5H), 2.36 (s, 3H), 2.58 (t, 4H, J=4.5Hz), 3.17 (t, 4H, J=4.5 Hz), 3.21-3.40 (m, 1H), 3.64 (d, 1H, J=9.0 Hz),6.88 (d, 2H, J=9.0 Hz), 7.01 (s, 1H), 7.37 (d, 2H, J=9.0 Hz).

I-53

mp:>300° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.20-1.54 (m, 4H), 1.27 (s, 9H),1.73-1.88 (m, 2H), 1.89-2.01 (m, 2H), 2.13-2.25 (m, 1H), 2.98-3.12 (m,1H), 3.15-3.31 (m, 8H), 6.76-6.84 (m, 2H), 6.93 (d, 2H, J=9.0 Hz), 6.99(d, 2H, J=8.1 Hz), 7.24 (d, 2H, J=8.1 Hz), 7.46 (d, 2H, J=9.0 Hz), 9.60(s, 1H).

I-54

mp:>215° C. (dec.); ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.27-2.00 (m,18H), 2.14-2.26 (m, 1H), 2.53-2.84 (m, 4H), 2.86-3.30 (m, 2H), 3.46-3.54(m, 1H), 3.62-3.74 (m, 2H), 6.78 (d, 1H, J=8.7 Hz), 6.87 (d, 2H, J=7.8Hz), 7.42 (d, 2H, J=8.7 Hz), 9.58 (s, 1H).

I-55

mp:>290° C. (dec.); ¹H-NMR (CDCl₃) δ ppm: 1.23-1.40 (m, 2H), 1.40 (s,9H), 1.60-1.76 (m, 2H), 2.02-2.27 (m, 5H), 3.20 (t, 4H, J=5.4 Hz),3.21-3.32 (m, 1H), 3.67 (d, 1H, J=9.3 Hz), 3.98 (t, 4H, J=4.8 Hz), 6.52(t, 1H, J=4.8 Hz), 6.93 (d, 2H, J=8.4 Hz), 7.06 (s, 1H), 7.41 (d, 2H,J=8.7 Hz), 8.33 (d, 2H, J=4.8 Hz).

I-56

mp:>232° C. (dec.); ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.27-1.48 (m,4H), 1.80-1.99 (m, 4H), 2.14-2.25 (m, 1H), 3.04-3.24 (m, 8H), 3.68 (s,3H), 3.76 (s, 3H), 6.44-6.47 (m, 1H), 6.66 (s, 1H), 6.76-6.84 (m, 2H),6.92 (d, 2H, J=8.4 Hz), 7.46 (d, 2H, J=8.4 Hz), 9.61 (s, 1H).

I-57

mp: 284-285° C. (dec.); ¹H-NMR (CDCl₃) δ ppm: 1.27 (t, 3H, J=7.2 Hz),1.40 (s, 9H), 1.61-2.24 (m, 9H), 2.35-2.49 (m, 1H), 2.76 (t, 2H, J=10.2Hz), 3.04-3.15 (m, 2H), 3.20-3.36 (m, 1H), 3.55-3.59 (m, 2H), 3.87 (d,1H, J=9.6 Hz), 4.12-4.19 (m, 2H), 6.90 (d, 2H, J=8.7 Hz), 2.79 (s, 1H),7.40 (d, 2H, J=8.7 Hz).

I-58

mp:>299° C. (dec.); ¹H-NMR (CDCl₃) δ ppm: 1.26-1.33 (m, 2H), 1.40 (s,9H), 1.56-2.42 (m, 19H), 2.73-2.81 (m, 4H), 3.16-3.26 (m, 4H), 3.64 (d,1H, J=9.6 Hz), 6.87 (d, 2H, J=8.7 Hz), 7.04 (s, 1H), 7.37 (d, 2H, J=9.0Hz).

I-59

mp:>270° C. (dec.); ¹H-NMR (CDCl₃) δ ppm: 1.26-1.47 (m, 2H), 1.47 (s,9H), 1.60-1.80 (m, 4H), 2.01-2.32 (m, 5H), 3.28-3.40 (m, 3H), 3.62-3.74(m, 3H), 5.74-5.96 (m, 2H), 6.92 (d, 2H, J=8.7 Hz), 7.13 (s, 1H), 7.39(d, 2H, J=9.0 Hz).

I-60

mp: 247-250° C. (dec.); ¹H-NMR (CDCl₃) δ ppm: 1.20-1.37 (m, 2H), 1.40(s, 9H), 1.60-1.78 (m, 2H), 1.98-2.33 (m, 5H), 2.93-3.03 (m, 2H),3.22-3.40 (m, 1H), 3.52 (t, 2H, J=6.0 Hz), 3.62 (d, 1H, J=8.4 Hz), 4.36(s, 2H), 6.93 (d, 2H, J=8.7 Hz), 7.00 (s, 1H), 7.11.-7.22 (m, 4H), 7.39(d, 2H, J=8.7 Hz).

I-61

mp: 280-281° C. ¹H-NMR (CDCl₃) δ ppm: 1.21-1.38 (m, 2H), 1.41 (s, 9H),1.64-1.80 (m, 2H), 2.02-2.33 (m, 5H), 3.24-3.40 (m, 1H), 3.61 (d, 1H,J=9.0 Hz), 6.33 (t, 2H, J=2.1 Hz), 7.04 (t, 2H, J=2.1 Hz), 7.14 (s, 1H),7.34 (d, 2H, J=9.0 Hz), 7.56 (d, 2H, J=9.0 Hz).

I-62

mp: 260-262° C. ¹H-NMR (CDCl₃) δ ppm: 1.22-1.39 (m, 2H), 1.41 (s, 9H),1.64-1.82 (m, 2H), 2.02-2.35 (m, 5H), 3.24-3.40 (m, 1H), 3.62 (d, 1H,J=9.6 Hz), 7.31 (d, 2H, J=9.0 Hz), 7.51 (s, 1H), 7.69 (d, 2H, J=9.0 Hz).

I-63

mp: 248° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.38 (m, 2H), 1.40 (s, 9H),1.61-1.78 (m, 2H), 1.98-2.32 (m, 5H), 3.22-3.45 (m, 1H), 3.64 (d, 1H,J=9.3 Hz), 7.11 (s, 1H), 7.37-7.46 (m, 4H).

I-64

mp: 272-275° C. (dec.); ¹H-NMR (DMSO-d₆) δ ppm: 1.20-1.53 (m, 4H), 1.27(s, 9H), 1.75-1.88 (m, 2H), 1.88-2.00 (m, 2H), 2.11-2.24 (m, 1H),2.96-3.12 (m, 1H), 5.96 (s, 2H), 6.77 (d, 1H, J=8.7 Hz), 6.82 (d, 1H,J=8.4 Hz), 6.95 (dd, 1H, J=1.8, 8.4 Hz), 7.29 (d, 1H, J=1.8 Hz), 9.70(s, 1H).

I-65

mp: 293-296° C. (dec.); ¹H-NMR (DMSO-d₆) δ ppm: 1.20-1.70 (m, 10H), 1.27(s, 9H), 1.79-2.038 (m, 4H), 2.18-2.33 (m, 1H), 2.98-3.30 (m, 5H), 6.79(d, 1H, J=9.0 Hz), 6.97 (d, 2H, J=8.1 Hz), 7.43-7.57 (m, 4H), 7.62 (d,2H, J=8.1 Hz), 9.82 (s, 1H).

I-66

mp:>300° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.27-1.53 (m, 4H),1.86-1.99 (m, 4H), 2.22-2.34 (m, 1H), 2.39 (s, 3H), 3.00-3.14 (m, 1H),6.25 (s, 1H), 6.79 (d, 1H, J=9.0 Hz), 7.47-7.50 (m, 1H), 7.69-7.76 (m,1H), 10.27 (s, 1H).

I-67

mp: 248-249° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.20-1.54 (m, 4H), 1.27 (s, 9H),1.77-1.90 (m, 2H), 1.90-2.02 (m, 2H), 2.02 (s, 3H), 2.17-2.32 (m, 1H),2.96-3.13 (m, 1H, 6.78 (d, 1H, J=8.7 Hz), 7.12-7.30 (m, 3H), 7.89 (s,1H), 9.79 (s, 1H), 9.88 (s, 1H).

I-68

mp:>300° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.20-1.54 (m, 4H), 1.27 (s, 9H),1.77-1.89 (m, 2H), 1.89-2.03 (m, 2H), 2.00 (s, 3H), 2.14-2.28 (m, 1H),2.95-3.13 (m, 1H), 6.78 (d, 1H, J=8.7 Hz), 7.40-7.54 (m, 4H), 9.72 (s,1H), 9.83 (s, 1H).

I-69

mp: 199-201° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.21-1.53 (m, 4H), 1.27 (s, 9H),1.76-1.89 (m, 2H), 1.89-2.02 (m, 2H), 2.13-2.30 (m, 1H), 2.85 (s, 6H),2.94-3.14 (m, 1H), 6.40 (dd, 1H, J=2.4, 8.4 Hz), 6.78 (d, 1H, J=8.7 Hz),6.90 (d, 1H, J=8.4 Hz), 7.05 (t, 2H, J=8.4 Hz), 9.60 (s, 1H).

I-70

mp: 227-230° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.22-1.52 (m, 4H), 1.27 (s, 9H),1.72-1.87 (m, 2H), 1.87-2.01 (m, 2H), 2.12-2.29 (m, 1H), 2.96-3.12 (m,1H), 5.00 (s, 2H), 6.22 (d, 1H, J=7.5 Hz), 6.66 (d, 1H, J=7.5 Hz), 6.78(d, 1H, J=9.0 Hz), 6.86 (d, 1H, J=7.5 Hz), 6.89-6.95 (m, 1H), 9.46 (s,1H).

I-71

mp: 270-272° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.22-1.52 (m, 4H), 1.26 (s, 9H),1.73-1.86 (m, 2H), 1.88-2.00 (m, 2H), 2.08-2.22 (m, 1H), 2.95-3.11 (m,1H), 4.80 (s, 2H), 6.47 (d, 2H, J=8.4 Hz), 6.77 (d, 1H, J=8.4 Hz), 7.20(d, 2H, J=8.4 Hz), 9.35 (s, 1H).

I-72

mp: 262-263° C. ¹H-NMR (CDCl₃) δ ppm: 1.25 (d, 6H, J=6.3 Hz), 1.17-1.42(m, 2H), 1.40 (s, 9H), 1.60-1.78 (m, 2H), 1.98-2.43 (m, 7H), 3.20-3.43(m, 3H), 3.67 (d, 1H, J=9.6 Hz), 3.74-3.86 (m, 2H), 6.86 (d, 2H, J=9.0Hz), 7.04 (s, 1H), 7.38 (d, 2H, J=9.0 Hz).

I-73

mp: 218-219° C. ¹H-NMR (CD₃OD) δ ppm: 1.36 (s, 9H), 1.36-1.69 (m, 4H),1.45 (s, 9H), 1.88-2.02 (m, 3H), 2.06-2.30 (m, 4H), 3.05-3.44 (m, 3H),3.46-3.56 (m, 1H), 4.16-4.26 (m, 1H), 6.51 (d, 2H, J=9.0 Hz), 7.30 (d,2H, J=8.7 Hz).

I-74

mp: 295-296° C. (dec.); ¹H-NMR (CD₃OD) δ ppm: 1.36 (s, 9H), 1.36-1.67(m, 4H), 1.92-2.13 (m, 4H), 2.26-2.40 (m, 2H), 2.62-2.75 (m, 1H),3.16-3.25 (m, 1H), 3.58-3.98 (m, 4H), 4.16-4.25 (m, 1H), 7.20-7.30 (m,2H), 7.62 (d, 2H, J=9.0 Hz).

I-75

mp: 250-251° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.23-1.55 (m, 4H), 1.27 (s, 9H),1.78-1.90 (m, 2H), 1.90-2.02 (m, 2H), 2.15-2.28 (m, 1H), 2.98-3.14 (m,1H), 3.06 (t, 2H, J=8.4 Hz), 3.87 (t, 2H, J=8.4 Hz), 6.67 (dd, 1H,J=1.5, 7.2 Hz), 6.80 (d, 1H, J=8.4 Hz), 6.94-7.05 (m, 2H), 7.12-7.19 (m,1H), 7.16 (d, 2H, J=9.3 Hz), 7.57 (d, 2H, J=9.3 Hz), 9.73 (s, 1H).

I-76

mp: 265-266° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.23-1.58 (m, 4H), 1.28 (s, 9H),1.83-2.04 (m, 4H), 2.20-2.36 (m, 1H), 2.97-3.16 (m, 1H), 6.67 (d, 1H,J=3.0 Hz), 6.82 (d, 1H, J=8.4 Hz), 7.07-7.22 (m, 2H), 7.47-7.53 (m, 1H),7.50 (d, 2H, J=9.0 Hz), 7.58 (d, 1H, J=3.0 Hz), 7.64 (d, 1H, J=7.5 Hz),7.79 (d, 2H, J=9.0 Hz), 10.02 (s, 1H).

I-77

mp: 281° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.21-1.56 (m, 4H), 1.27 (s, 9H),1.80-2.03 (m, 4H), 2.18-2.31 (m, 1H), 2.97-3.14 (m, 1H), 6.51 (dd, 1H,J=2.1, 2.7 Hz), 6.81 (d, 1H, J=9.0 Hz), 7.67-7.78 (m, 5H), 8.41 (d, 1H,J=2.1 Hz), 9.96 (s, 1H).

I-78

mp:>300° C. (dec.); ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.27-1.52 (m,4H), 1.74-2.04 (m, 7H), 2.10-2.25 (m, 2H), 2.96-3.20 (m, 2H), 3.48-3.58(m, 1H), 3.75-3.84 (m, 1H), 6.39 (d, 2H, J=8.4 Hz), 6.79 (d, 1H, J=8.4Hz), 7.02 (s, 1H), 7.30 (s, 1H), 7.36 (d, 2H, J=8.1 Hz), 9.48 (s, 1H).

I-79

mp: 248-250° C. (dec.); ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.27-1.54(m, 4H), 1.85-1.99 (m, 4H), 2.24-2.33 (m, 1H), 3.00-3.14 (m, 1H), 6.82(d, 1H, J=8.7 Hz), 7.77 (d, 2H, J=8.4 Hz), 8.07 (d, 2H, J=8.4 Hz).

I-80

mp:>300° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.22-1.58 (m, 4H), 1.27 (s, 9H),1.80-2.03 (m, 4H), 2.18-2.32 (m, 1H), 2.98-3.14 (m, 1H), 6.80 (d, 1H,J=8.7 Hz), 7.35-7.50 (m, 2H), 7.99 (s, 1H), 8.11 (s, 1H), 9.79 (s, 1H),12.94 (s, 1H).

I-81

mp: 261-262° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.21-1.57 (m, 4H), 1.27 (s, 9H),1.78-2.02 (m, 4H), 2.17-2.30 (m, 1H), 2.96-3.16 (m, 1H), 6.34 (s, 1H),6.80 (d, 1H, J=8.7 Hz), 7.14-7.32 (m, 3H), 7.85 (s, 1H), 9.58 (s, 1H),10.95 (s, 1H).

I-82 ¹H-NMR (CDCl₃) δ ppm: 0.86 (s, 18H), 1.24-1.37 (m, 2H), 1.37 (s,9H), 1.56-1.74 (m, 2H), 1.95-2.19 (m, 5H), 3.18-3.32 (m, 1H), 3.44 (t,4H, J=6.3 Hz), 3.70 (t, 4H, J=6.3 Hz), 4.39 (d, 1H, J=9.0 Hz), 6.59 (d,2H, J=9.0 Hz), 7.31 (d, 2H, J=8.7 Hz), 7.43 (s, 1H).

I-83

mp: 264-265° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.27-1.52 (m, 4H),1.78-1.88 (m, 2H), 1.90-2.00 (m, 2H), 2.14-2.26 (m, 1H), 2.96-3.14 (m,1H), 6.72-6.82 (m, 2H), 6.99 (t, 4H, J=7.8 Hz), 7.18 (t, 2H, J=7.5 Hz),7.46 (d, 2H, J=9.0 Hz), 8.00 (s, 1H), 9.65 (s, 1H).

I-84

mp: 27° C. (dec.); ¹H-NMR (DMSO-d₆) δ ppm: 1.23-1.57 (m, 4H), 1.27 (s,9H), 1.83-2.03 (m, 4H), 2.23-2.35 (m, 1H), 2.98-3.15 (m, 1H), 6.80 (d,1H, J=8.1 Hz), 7.87 (d, 2H, J=9.0 Hz), 8.34 (d, 2H, J=9.0 Hz), 9.21 (s,1H), 10.20 (s, 1H).

I-85

mp: 256-258° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.22-1.53 (m, 4H), 1.26 (s, 9H),1.79-2.01 (m, 4H), 2.25 (s, 3H), 2.28-2.42 (m, 1H), 2.97-3.02 (m, 1H),6.71 (d, 1H, J=0.9 Hz), 6.80 (d, 1H, J=8.1 Hz), 11.91 (s, 1H).

I-86

mp: 228-230° C. ¹H-NMR (CD₃OD) δ ppm: 1.36 (s, 9H), 1.36-1.48 (m, 2H),1.55-1.70 (m, 2H), 1.87-1.98 (m, 2H), 2.08-2.17 (m, 2H), 2.20-2.32 (m,1H), 3.15-3.27 (m, 1H), 3.50 (t, 4H, J=5.7 Hz), 3.69 (t, 4H, J=5.7 Hz),6.72 (d, 2H, J=9.0 Hz), 7.29-7.33 (m, 2H).

I-87

mp: 183-184° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.27-1.48 (m, 4H),1.73-1.89 (m, 4H), 1.90-2.00 (m, 2H), 2.16-2.28 (m, 1H), 2.28 (t, 2H,J=7.5 Hz), 2.51-2.54 (m, 2H), 2.97-3.13 (m, 1H), 3.58 (s, 3H), 6.79 (d,1H, J=8.7 Hz), 7.08 (d, 2H, J=8.7 Hz), 7.49 (d, 2H, J=8.4 Hz), 9.73 (s,1H).

I-88

mp: 217-218° C. ¹H-NMR (CD₃OD) δ ppm: 1.36 (s, 9H), 1.36-1.46 (m, 2H),1.55-1.69 (m, 2H), 1.83-2.00 (m, 4H), 2.07-2.18 (m, 2H), 2.26-2.36 (m,3H), 2.61 (t, 2H, J=7.5 Hz), 3.14-3.26 (m, 1H), 7.13 (d, 2H, J=8.1 Hz),7.44 (d, 2H, J=8.1 Hz).

I-89

¹H-NMR (CDCl₃) δ ppm: 0.08 (d, 6H, J=3.3 Hz), 0.88 (s, 9H), 1.21-1.36(m, 2H), 1.39 (s, 9H), 1.61-1.74 (m, 2H, 1.88-2.23 (m, 6H), 3.06-3.11(m, 1H), 3.24-3.74 (m, 4H), 3.92 (d, 1H, J=9.6 Hz), 4.48-4.56 (m, 1H),6.47 (d, 2H, J=9.0 Hz), 7.17 (s, 1H), 7.32 (d, 2H, J=9.0 Hz).

I-90

mp: amorphous ¹H-NMR (CD₃OD) δ ppm: 1.36 (s, 9H), 1.36-1.47 (m, 2H),1.56-1.70 (m, 3H), 1.88-2.30 (m, 6H), 3.05-3.49 (m, 5H), 4.50 (brs, 1H),6.50 (d, 2H, J=9.0 Hz), 7.29 (d, 2H, J=9.0 Hz).

I-91

mp: 105-106° C. ¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=7.3 Hz), 1.25-1.27(m, 2H), 1.36 (d, 6H, J=6.9 Hz), 1.51-1.59 (m, 2H), 2.56 (t, 2H, J=7.8Hz), 3.27 (sept, 1H, J=6.9 Hz), 7.12 (d, 2H, J=8.6 Hz), 7.32 (t, 1H,J=7.8 Hz), 7.45 (brd, 1H, J=7.8 Hz), 7.53 (d, 2H, J=8.6 Hz), 7.58 (d,1H, J=7.8 Hz), 7.71-7.72 (m, 2H), 8.27 (s, 1H).

I-92

mp: 163-164° C. ¹H-NMR (CDCl₃) δ ppm: 0.93 (t, 3H, J=7.3 Hz), 1.32-1.39(m, 2H), 1.55-1.65 (m, 2H), 1.87 (s, 3H), 1.95 (s, 3H), 2.60 (t, 2H,J=7.6 Hz), 7.07 (d, 2H, J=8.4 Hz), 7.18 (d, 2H, J=8.5 Hz), 7.54 (d, 2H,J=8.5 Hz), 7.91 (brs, 1H), 8.18 (d, 2H, J=8.4 Hz), 8.77 (s, 1H).

I-93

mp: 173° C. ¹H-NMR (CDCl₃) δ ppm: 0.93 (t, 3H, J=7.3 Hz), 1.32-1.40 (m,2H), 1.39 (d, 6H, J=6.9 Hz), 1.55-1.62 (m, 2H), 2.60 (t, 2H, J=7.8 Hz),3.13 (sept, 1H, J=6.9 Hz), 4.39 (d, 2H, J=6.3 Hz), 4.45 (t, 1H, J=6.3Hz), 7.18 (d, 2H, J=8.7 Hz), 7.46 (d, 2H, J=8.7 Hz), 7.54 (d, 2H, J=8.7Hz), 7.80 (s, 1H), 7.85 (d, 2H, J=8.7 Hz).

I-94

mp: 159-160° C. ¹H-NMR (CDCl₃) δ ppm: 0.93 (t, 3H, J=7.3 Hz), 1.32-1.39(m, 2H), 1.54-1.80 (m, 2H), 1.79 (s, 3H), 1.80 (s, 3H), 2.60t, 2H, J=7.7Hz), 3.18 (s, 3H), 7.18 (d, 2H, J=8.5 Hz), 7.30 (d, 2H, J=8.8 Hz), 7.52(d, 2H, J=8.5 Hz), 7.70 (brs, 1H), 7.84 (d, 2H, J=8.8 Hz), 8.77 (s, 1H).

I-95

mp: 177-178° C. ¹H-NMR (CDCl₃) δ ppm: 0.94 (t, 3H, J=7.2 Hz), 1.31-1.48(m, 8H), 1.54-1.66 (m, 2H), 2.55 (s, 3H), 2.62 (t, 2H, J=7.6 Hz), 3.92(sept, 1H, J=6.6 Hz), 7.20 (d, 2H, J=8.45 Hz), 7.74 (d, 2H, J=8.5 Hz),9.01 (brs, 1H), 9.17 (s, 1H).

I-96

mp: 220-223° C. ¹H-NMR (CDCl₃) δ ppm: 0.93 (t, 3H, J=7.3 Hz), 1.28-1.42(m, 2H), 1.50 (d, 6H, J=6.8 Hz), 1.54-1.65 (m, 2H), 2.62 (t, 2H, J=7.6Hz), 4.08 (sept, 1H, J=7.1 Hz), 7.20 (d, 2H, J=8.5 Hz), 7.48 (d, 2H,J=8.5 Hz), 7.71 (brs, 1H), 8.51 (brs, 1H), 8.95 (s, 1H).

I-97

mp: 195-197° C. ¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.6 Hz), 0.94 (t,3H, J=7.3 Hz), 1.32-1.44 (m, 6H), 1.54-1.64 (m, 2H), 1.66-1.78 (m, 2H),2.62 (t, 2H, J=7.7 Hz), 2.86 (brs, 2H), 3.98 (sept, 1H, J=7.1 Hz), 7.19(d, 2H, J=8.5 Hz), 7.63 (d, 2H, J=8.4 Hz), 8.72 (brs, 1H), 8.81 (brs,1H).

I-98

mp: 216-218° C. ¹H-NMR (CDCl₃+CD₃OD) δ ppm: 0.93 (t, 3H, J=7.4 Hz),1.29-1.40 (m, 2H), 1.43 (d, 2H), J=6.9 Hz), 1.51-1.63 (m, 2H), 2.60 (t,2H, J=7.8 Hz), 3.65 (sept, 1H, J=6.9 Hz), 7.18 (d, 2H, J=8.5 Hz), 7.22(d, 1H, J=8.8 Hz), 7.55 (d, 2H, J=8.5 Hz), 8.18 (dd, 1H, J=8.8, 2.4 Hz),8.63 (d, 1H, J=2.4 Hz).

I-99

mp: 201-202° C. ¹H-NMR (CDCl₃) δ ppm: 0.93 (t, 3H, J=7.3 Hz), 1.22-1.40(m, 2H), 1.49 (d, 2H, J=7.1 Hz), 1.51-1.63 (m, 2H), 2.59 (t, 2H, J=7.7Hz), 4.22 (sept, 1H, J=7.1 Hz), 7.16 (d, 2H, J=8.4 Hz), 7.41 (brs, 1H),7.52 (d, 2H, J=8.4 Hz), 8.10 (brs, 1H), 8.13 (d, 1H, J=2.2 Hz), 8.61(brs, 1H).

I-100

mp: 160-162° C. ¹H-NMR (CDCl₃) δ ppm: 0.93 (t, 3H, J=7.3 Hz), 1.22-1.42(m, 2H), 1.45 (d, 2H, J=6.9 Hz), 1.51-1.63 (m, 2H), 2.61 (t, 2H, J=7.8Hz), 3.37 (sept, 1H, J=6.9 Hz), 6.89 (brs, 1H), 7.19 (d, 2H, J=8.4 Hz),7.65 (d, 2H, J=8.4 Hz), 7.80 (dd, 1H, J=8.4, 2.4 Hz), 8.27 (d, 1H, J=8.4Hz), 8.45 (d, 1H, J=2.4 Hz), 9.75 (brs, 1H).

I-101, I-214

mp: 192-194° C. ¹H-NMR (CDCl₃) δ ppm: 0.93 (t, 3H, J=7.3 Hz), 1.27-1.41(m, 2H), 1.35 (s, 9H), 1.50-1.66 (m, 2H), 2.60 (t, 2H, J=7.6 Hz), 5.58(brs, 1H), 7.07 (d, 2H, J=8.5 Hz), 7.17 (d, 2H, J=8.5 Hz), 7.52 (d, 2H,J=8.5 Hz), 7.71 (brs, 1H), 7.79 (d, 2H, J=8.5 Hz).

I-102

mp: 216-217° C. ¹H-NMR (CDCl₃) δ ppm: 0.93 (t, 3H, J=7.3 Hz), 1.26-1.42(m, 2H), 1.45 (s, 9H), 1.70-1.83 (m, 2H), 2.60 (t, 2H, J=7.7 Hz), 6.42(brs, 1H), 7.18 (d, 2H, J=8.5 Hz), 7.35 (d, 2H, J=8.5 Hz), 7.51 (d, 2H,J=8.5 Hz), 7.68 (brs, 1H), 7.82 (d, 2H, J=8.5 Hz).

I-103

¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.3 Hz), 1.28-1.36 (m, 2H), 1.32(d, 6H, J=6.9 Hz), 1.49-1.59 (m, 2H), 2.54 (t, 2H, J=7.7 Hz), 3.23(sept, 1H, J=6.9 Hz), 3.46 (s, 3H), 6.76 (brs, 1H), 6.91 (d, 2H, J=8.2Hz), 6.99 (d, 2H, J=8.8 Hz), 7.03 (d, 2H, J=8.2 Hz), 7.25 (d, 2H, J=8.8Hz).

I-104

mp: 182-183° C. ¹H-NMR (CDCl₃) δ ppm: 0.93 (t, 3H, J=7.3 Hz), 1.28-1.40(m, 2H), 1.51-1.63 (m, 2H), 1.64-1.88 (m, 4H), 1.90-2.23 (m, 4H), 2.60(t, 2H, J=7.6 Hz), 3.39 (m, 1H), 6.16 (brs, 1H), 7.07 (d, 2H, J=8.5 Hz),7.16 (d, 2H, J=8.5 Hz), 7.52 (d, 2H, J=8.5 Hz), 7.74 (brs, 1H), 7.77 (d,2H, J=8.5 Hz).

I-105

mp: 190-191° C. ¹H-NMR (CDCl₃) δ ppm: 0.93 (t, 3H, J=7.3 Hz), 1.28-1.41(m, 2H), 1.52-1.69 (m, 4H), 1.75-1.90 (m, 2H), 1.92-2.07 (m, 4H), 2.58(t, 2H, J=7.6 Hz), 3.59 (m, 1H), 6.53 (brs, 1H), 7.18 (d, 2H, J=8.5 Hz),7.31 (d, 2H, J=8.5 Hz), 7.52 (d, 2H, J=8.5 Hz), 7.67 (brs, 1H), 7.84 (d,2H, J=8.5 Hz).

I-106

mp: 194-197° C. ¹H-NMR (CDCl₃) δ ppm: 0.93 (t, 3H, J=7.3 Hz), 1.22-1.41(m, 2H), 1.53-1.65 (m, 2H), 1.90 (s, 6H), 2.60 (t, 2H, J=7.8 Hz), 6.86(brs, 1H), 7.18 (d, 2H, J=8.5 Hz), 7.43 (d, 2H, J=8.5 Hz), 7.51 (d, 2H,J=8.5 Hz), 7.71 (brs, 1H), 7.84 (d, 2H, J=8.5 Hz).

I-107

mp: 211-212° C. ¹H-NMR (CDCl₃) δ ppm: 0.93 (t, 3H, J=7.3 Hz), 1.24-1.40(m, 2H), 1.50-1.62 (m, 2H), 2.60 (t, 2H, J=7.6 Hz), 6.19 (brs, 1H), 7.17(d, 2H, J=8.5 Hz), 7.18 (d, 2H, J=8.5 Hz), 7.51 (d, 2H, J=8.5 Hz), 7.66(brs, 1H), 7.86 (d, 2H, J=8.5 Hz).

I-108

mp: 298-300° C. ¹H-NMR (DMSO-d₆) δ ppm: 0.90 (t, 3H, J=7.3 Hz),1.22-1.39 (m, 2H), 1.48-1.60 (m, 2H), 2.54 (t, 2H, J=7.3 Hz), 7.04 (d,2H, J=8.8 Hz), 7.12 (d, 2H, J=8.5 Hz), 7.64 (d, 2H, J=8.5 Hz), 7.69 (d,2H, J=8.8 Hz), 9.80 (s, 1H).

I-109

mp: 122-123° C. ¹H-NMR (CDCl₃) δ ppm: 0.90 (t, 3H, J=7.4 Hz), 0.97 (t,3H, J=7.7 Hz), 1.26-1.38 (m, 2H), 1.30 (s, 6H), 1.50-1.66 (m, 4H),1.72-1.83 (m, 4H), 2.34 (t, 2H, J=7.1 Hz), 2.55 (t, 2H, J=7.6 Hz), 3.19(q, 1H, J=6.0 Hz), 4.60 (brs, 1H), 7.08 (d, 2H, J=8.5 Hz), 7.42 (d, 2H,J=8.5 Hz), 7.85 (s, 1H).

I-110

mp: 109-110° C. ¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.4 Hz), 1.10 (d,6H, J=6.7 Hz), 1.29-1.38 (m, 2H), 1.55 (s, 9H), 1.60-1.70 (m, 2H),1.78-1.89 (m, 2H), 2.26 (m, 1H), 2.39 (t, 2H, J=7.0 Hz), 2.57 (t, 2H,J=7.7 Hz), 2.90 (d, 2H, J=6.6 Hz), 3.16 (brs, 1H), 4.24 (brs, 1H), 7.12(d, 2H, J=8.5 Hz), 7.40 (d, 2H, J=8.5 Hz).

I-111

mp: 64-65° C. ¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.3 Hz), 1.02 (t, 3H,J=7.5 Hz), 1.35 (d, 3H, J=6.7 Hz), 1.26-1.38 (m, 2H), 1.48-1.69 (m, 5H),1.76-1.87 (m, 2H), 2.04 (m, 1H), 2.38 (t, 2H, J=7.3 Hz), 2.56 (t, 2H,J=7.6 Hz), 2.91 (m, 1H), 3.16 (brs, 2H), 4.42 (brs, 1H), 7.11 (d, 2H,J=8.5 Hz), 7.42 (d, 2H, J=8.5 Hz), 7.47 (brs, 1H).

I-112

mp: 79-80° C. ¹H-NMR (CDCl₃) δ ppm: 1.36 (s, 9H), 1.52-1.62 (m, 2H),1.67-1.76 (m, 2H), 2.22 (t, 2H, J=7.4 Hz), 3.16 (q, 2H, J=6.3 Hz), 3.78(s, 3H), 4.33 (d, 2H, J=5.4 Hz), 4.62 (brs, 1H), 6.20 (brs, 1H), 6.85(d, 2H, J=8.8 Hz), 7.19 (d, 2H, J=8.8 Hz).

I-113

mp: 125-126° C. ¹H-NMR (CDCl₃) δ ppm: 1.38 (s, 9H), 1.62-1.70 (m, 2H),1.76-1.88 (m, 2H), 2.46 (t, 2H, J=7.4 Hz), 3.22 (q, 2H, J=6.1 Hz), 4.22(t, 1H, J=6.1 Hz), 7.24 (dd, 1H, J=8.9, 2.3 Hz), 7.36 (d, 1H, J=2.3 Hz),7.65 (brs, 1H), 8.29 (d, 1H, J=8.9 Hz).

I-114

mp: 89-91° C. ¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=7.0 Hz), 1.06 (d, 6H,J=7.0 Hz), 1.36 (m, 1H), 1.50-1.72 (m, 5H), 1.94-2.06 (m, 2H), 2.26 (m,1H), 2.60 (t, 2H, J=7.7 Hz), 2.84 (t, 2H, J=7.7 Hz), 2.93 (d, 2H, J=6.3Hz), 3.20 (t, 2H, J=6.6 Hz), 4.30 (brs, 1H), 7.19 (d, 2H, J=8.5 Hz),7.63 (d, 2H, J=8.5 Hz), 9.15 (brs, 1H).

I-115

mp: 94-95° C. ¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=7.5 Hz), 1.03 (t, 3H,J=7.5 Hz), 1.23-1.40 (m, 5H), 1.42-1.65 (m, 6H), 1.75 (m, 1H), 2.02 (m,1H), 2.24 (t, 2H, J=7.0 Hz), 2.59 (t, 2H, J=8.0 Hz), 2.90 (m, 1H), 3.14(q, 2H, J=6.6 Hz), 4.20 (m, 1H), 4.40 (d, 2H, J=5.4 Hz), 5.70 (brs, 1H),7.14 (d, 2H, J=8.1 Hz), 7.18 (d, 2H, J=8.1 Hz).

I-116

mp: 89-91° C. ¹H-NMR (CDCl₃) δ ppm: 0.97 (t, 3H, J=7.3 Hz), 1.02 (t, 31,J=7.5 Hz), 1.35 (d, 3H, J=7.0 Hz), 1.40-1.90 (m, 9H), 2.04 (m, 1H), 2.37(t, 2H, J=7.0 Hz), 2.90 (m, 1H), 3.17 (q, 2H, J=6.6 Hz), 3.93 (t, 2H,J=6.6 Hz), 4.32 (m, 1H), 6.84 (d, 2H, J=9.0 Hz), 7.31 (brs, 1H), 7.40(d, 2H, J=9.0 Hz).

I-117

mp: 110-111° C. ¹H-NMR (CDCl₃) δ ppm: 1.02 (t, 3H, J=7.5 Hz), 1.34 (d,3H, J=6.6 Hz), 1.45-1.70 (m, 3H), 1.75-1.85 (m, 2H), 2.05 (m, 1H), 2.36(t, 2H, J=7.5 Hz), 2.90 (m, 1H), 3.16 (q, 2H, J=6.6 Hz), 3.78 (s, 3H),4.50 (m, 1H), 6.84 (d, 2H, J=6.8 Hz), 7.42 (d, 2H, J=6.8 Hz), 7.48 (brs,1H).

I-118

mp: 113-115° C. ¹H-NMR (CDCl₃) δ ppm: 0.92 (t, 3H, J=7.0 Hz), 1.20-1.34(m, 1H), 1.37 (d, 6H, J=7.0 Hz), 1.48-1.70 (m, 3H), 2.43 (q, 2H, J=6.6Hz), 2.58 (t, 2H, J=7.7 Hz), 3.10-3.31 (m, 3H), 4.75 (m, 1H), 6.04 (d,1H, J=15.0 Hz), 6.77 (dt, 1H, J=7.7, 15.0 Hz), 7.14 (d, 2H, J=8.4 Hz),7.55 (d, 2H, J=8.4 Hz), 7.85 (brs, 1H).

I-119

mp: 139-140° C. ¹H-NMR (CDCl₃) δ ppm: 1.19 (s, 9H), 1.47 (m, 2H), 1.61(m, 2H), 2.18 (t, 2H, J=7.6 Hz), 3.03 (q, 2H, J=6.3 Hz), 4.09 (t, 1H,J=5.9 Hz), 6.85 (brd, 1H, J=8.0 Hz), 7.00 (t, 1H, J=8.0 Hz), 7.16 (brd,1H, J=8.0), 7.48 (brs, 1H), 7.57 (brs, 1H).

I-120

mp: 183° C. ¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.3 Hz), 1.20-1.58 (m,61-1), 1.40 (s, 9H), 2.07 (dd, 1H, J=12.9, 3.1 Hz), 2.52 (t, 21H, J=7.7Hz), 2.95 (dd, 2H, J=11.5, 2.5Hz), 3.46 (m, 1H), 3.88-4.07 (m, 3H), 6.47(s, 1H), 7.08 (d, 2H, J=8.5 Hz), 7.22 (d, 2H, J=8.5 Hz).

I-121

mp: 163-166° C. ¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.3 Hz), 1.32-1.62(m, 6H), 1.45 (s, 9H), 1.95-2.07 (m, 3H), 2.20 (m, 1H), 2.46 (td, 1H,J=10.4, 3.7 Hz), 2.37 (t, 2H, J=7.6 Hz), 3.43 (brd, 2H, J=10.4 Hz), 4.80(s, 1H), 7.12 (d, 2H, J=8.4 Hz), 7.14 (s, 1H), 7.39 (d, 2H, J=8.4Hz).

I-122

mp: 188-189° C. ¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.25-1.41(m, 2H), 1.42 (s, 9H), 1.50-1.62 (m, 2H), 1.78-1.95 (m, 4H), 2.00-2.20(m, 6H), 2.57 (t, 2H, J=7.5 Hz), 3.99 (brs, 1H), 7.10 (brs, 1H), 7.12(d, 2H, J=6.5 Hz), 7.41 (d, 2H, J=6.5 Hz).

I-123

mp: 197-198° C. ¹H-NMR (CDCl₃) δ ppm: 0.91 (t, 3H, J=7.5 Hz), 1.24-1.40(m, 2H), 1.39 (s, 9H), 1.50-1.70 (m 2H), 1.99 (brs, 12H), 2.56 (t, 2H,J=7.5 Hz), 3.47 (brs, 1H), 7.10 (s, 1H), 7.11 (d, 2H, J=8.5 Hz), 7.38(d, 2H, J=8.5 Hz).

I-124

mp: 258-260° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.40 (m, 2H), 1.41 (s, 9H),1.62-1.81 (m, 2H), 2.03-2.35 (m, 5H), 2.37 (s, 3H), 2.71 (s, 3H), 3.32(m, 1H), 3.64 (d, 1H, J=8.4 Hz), 7.08 (brs, 1H), 7.24 (m, 1H), 7.33 (m,2H), 7.60 (d, 1H, J=8.1 Hz), 7.77 (s, 1H), 7.80 (d, 1H, J=8.4 Hz), 8.14(m, 1H).

I-125

mp: 297-299° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.28-1.56 (m, 4H),1.80-2.01 (m, 4H), 2.47 (m, 1H), 2.76 (brs, 1H), 3.05 (m, 2H), 6.78 (d,1H, J=9.0 Hz), 7.23 (d, 1H, J=9.0 Hz), 7.46 (dd, 1H, J=2.0, 9.0 Hz),8.03 (d, 1H, J=2.0 Hz).

I-126

mp: 198-199° C. ¹H-NMR (CDCl₃) δ ppm: 1.18-1.39 (m, 2H), 1.40 (s, 9H),1.60-1.79 (m, 2H), 1.98-2.35 (m, 5H), 3.30 (m, 1H), 3.67 (d, 1H, J=9.6Hz), 5.89 (tt, 1H, J=3.0, 50.0 Hz), 6.97 (d, 1H, J=7.8 Hz), 7.21 (s,1H), 7.30-7.40 (m, 2H), 7.55 (s, 1H).

I-127

mp: 262-264° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.39 (m, 2H), 1.41 (s, 9H),1.60-1.80 (m, 2H), 2.00-2.36 (m, 5H), 2.57 (s, 3H), 3.33 (m, 1H), 3.62(d, 1H, J=8.7 Hz), 7.28 (brs, 1H), 7.62 (d, 2H, J=8.7 Hz), 7.94 (d, 2H,J=8.7 Hz).

I-128

mp: 252-254° C. ¹H-NMR (CDCl₃) δ ppm: 1.18-1.39 (m, 2H), 1.40 (s, 9H),1.58-1.79 (m, 2H), 1.99-2.30 (m, 5H), 2.46 (s, 3H), 3.32 (m, 1H), 3.64(m, 1H), 7.11 (brs, 1H), 7.23 (d, 2H, J=9.0 Hz), 7.44 (d, 2H, J=9.0 Hz).

I-129

mp:>300° C. ¹H-NMR (CDCl₃+CD₃OD) δ ppm: 1.30-1.45 (m, 2H), 1.42 (s, 9H),1.70-1.88 (m, 2H), 2.10-2.37 (m, 4H), 2.52 (m, 1H), 3.34 (m, 1H),7.43-7.54 (m, 3H), 7.82 (d, 1H, J=6.7 Hz), 7.88 (d, 1H, J=8.5 Hz),7.98-8.07 (m, 2H), 8.44 (s, 1H), 8.46 (s, 1H).

I-130

mp: 123-124° C. ¹H-NMR (CDCl₃) δ ppm: 1.18-1.34 (m, 2H), 1.40 (s, 9H),1.62-1.75 (m, 2H), 2.00-2.28 (m, 5H), 3.31 (m, 1H), 3.61 (d, 1H, J=9.5Hz), 5.59 (s, 1H), 7.17 (s, 1H), 7.30-7.37 (m, 6H), 7.41 (d, 1H, J=8.5Hz), 7.84 (d, 1H, J=2.1 Hz).

I-131

mp: 202-204° C. ¹H-NMR (CDCl₃) δ ppm: 1.27-1.38 (m, 2H), 1.38 (s, 9H),1.62-1.75 (m, 2H), 1.97-2.04 (m, 2H), 2.18-2.27 (m, 3H), 3.26 (m, 1H),3.81 (s, 3H), 4.62 (d, 1H, J=7.9 Hz), 7.12 (d, 1H, J=7.8 Hz), 7.40 (t,1H, J=7.8 Hz), 7.51 (s, 3H), 7.61 (d, 1H, J=7.8 Hz), 7.71 (s, 1H), 8.21(brs, 1H).

I-132

mp: 236-237° C. ¹H-NMR (CDCl₃) δ ppm: 1.23-1.43 (m, 2H), 1.41 (s, 9H),1.66-1.80 (m, 2H), 2.08-2.12 (m, 2H), 2.23-2.31 (m, 3H), 3.34 (m, 1H),3.87 (d, 1H, J=9.5 Hz), 4.02 (s, 3H), 7.30 (td, 1H, J=1.1 Hz), 7.36 (s,1H), 7.39 (td, 1H, J=7.3, 1.5 Hz), 7.53 (brd, 1H, J=7.3 Hz), 7.84 (brd,1H, J=7.3 Hz), 8.05 (s, 1H), 8.73 (s, 1H).

I-133

mp: 198-200° C. ¹H-NMR (CDCl₃) δ ppm: 0.93 (t, 3H, J=7.3 Hz), 0.97 (t,3H, J=6.7 Hz), 1.18-1.81 (m, 7H), 1.39 (s, 9H), 1.98-2.05 (m, 2H),2.21-2.24 (m, 3H), 3.29 (m, 1H), 4.00 (dd, 1H, J=10.7, 6.7 Hz), 4.09(dd, 1H, J=10.7, 6.1 Hz), 4.27 (d, 1H, J=9.8 Hz), 6.37 (d, 1H, J=15.9Hz), 7.47 (d, 2H, J=8.5 Hz), 7.59 (d, 2H, J=8.5 Hz), 7.62 (d, 1H, J=15.9Hz), 7.83 (brs, 1H).

I-134

mp: 212-213° C. ¹H-NMR (CDCl₃) δ ppm: 1.21-1.32 (m, 2H), 1.39 (s, 9H),1.59-1.73 (m, 2H), 1.99-2.04 (m, 2H), 2.10-2.26 (m, 3H), 3.26 (m, 1H),3.72 (d, 1H, J=9.6 Hz), 6.74 (m, 1H), 7.02 (d, 2H, J=7.4 Hz), 7.11 (t,1H, J=7.4 Hz), 7.13-7.19 (m, 2H), 7.22-7.26 (m, 2H), 7.34 (t, 2H, J=7.4Hz).

I-135

mp: 294-296° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.28-1.55 (m, 4H),1.81-2.05 (m, 4H), 2.26 (m, 1H), 2.98-3.20 (m, 2H), 6.78 (d, 1H, J=9.0Hz), 7.31 (t, 1H, J=7.5 Hz), 7.54-7.72 (m, 5H), 7.94 (brs, 1H).

I-136

mp:>300° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.28 (s, 9H), 1.29-1.59 (m, 4H),1.81-2.02 (m, 4H), 2.27 (m, 1H). 3.06 (m, 1H), 6.81 (d, 1H, J=8.7 Hz),7.38 (t, 1H, J=7.2 Hz), 7.48 (t, 2H, J=7.2 Hz), 7.62-7.81 (m, 10H), 9.93(brs, 1H).

I-137

mp: 291-292° C. ¹H-NMR (CDCl₃) δ ppm: 1.25-1.39 (m, 2H), 1.41 (s, 9H),1.61-1.80 (m, 2H), 2.01-2.36 (m, 5H), 3.32 (m, 1H), 3.63 (d, 1H, J=9.3Hz), 7.20 (brs, 1H), 7.53-7.74 (m, 8H).

I-138

mp: 259-262° C. ¹H-NMR (CD₃OD) δ ppm: 1.40 (s, 9H), 1.40-1.80 (m, 4H),2.00-2.30 (m, 4H), 2.45 (m, 1H), 3.00 (s, 3H), 3.15-3.30 (m, 2H), 7.90(d, 1H, J=8.4 Hz), 8.12 (d, 1H, J=9.0 Hz), 8.39 (d, 1H, J=9.0 Hz), 8.72(s, 1H), 8.92 (d, 1H, J=8.4 Hz), 10.4 (s, 1H).

I-139

mp: 265-268° C. ¹H-NMR (CDCl₃) δ ppm: 1.25-1.40 (m, 2H), 1.40 (s, 9H),168-1.81 (m, 2H), 2.05-2.10 (m, 2H), 2.23-2.37 (m, 3H), 3.32 (m, 1H),4.27 (d, 1H, J=9.1 Hz), 7.53 (t, 1H, J=7.9 Hz), 7.63 (td, 1H, J=7.9, 1.4Hz), 7.77 (d, 1H, J=7.9 Hz), 8.03 (d, 1H, J=7.9 Hz), 8.37 (brs, 1H),8.85-8.86 (m, 2H).

I-140

mp: 258-260° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.40 (m, 2H), 1.41 (s, 9H),1.52-1.8.5 (m, 2H) 2.03-2.35 (m, 5H), 3.34 (m, 1H), 3.75 (m, 1H),7.35-7.66 (m, 3H), 8.05 (d, 1H, J=9.0 Hz), 8.11 (d, 1H, J=9.0 Hz), 8.40(brs, 1H), 8.83 (s, 1H).

I-141

mp: 205-206° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.37 (m, 2H), 1.40 (s, 9H),1.43-1.62 (m, 2H), 1.90-2.01 (m, 2H), 2.02-2.23 (m, 3H), 3.27 (m, 1H),3.63 (d, 1H, J=9.6 Hz), 3.70 (s, 3H), 6.64 (d, 1H, J=8.8 Hz), 7.28-7.41(m, 5H), 7.45 (brs, 1H), 8.26 (d, 1H, J=8.8 Hz).

I-142

mp: 277-280° C. ¹H-NMR (CDCl₃) δ ppm: 0.23-0.34 (m, 2H), 1.34 (s, 9H),1.34-1.55 (m, 5H), 1.76-1.80 (m, 2H), 2.97 (m, 1H), 3.31 (d, 1H, J=9.6Hz), 7.18 (s, 1H), 7.50-7.59 (m, 4H), 7.77 (dd, 1H, J=7.4, 1.0 Hz),7.91-7.98 (m, 2H), 8.39 (dd, 1H, J=7.4, 1.9 Hz).

I-143

mp: 202-203° C. ¹H-NMR (CDCl₃) δ ppm: 1.23-1.40 (m, 2H), 1.40 (s, 9H),1.57-1.71 (m, 2H), 2.05-2.10 (m, 2H), 2.18-2.28 (m, 3H), 3.31 (m, 1H),3.91 (s, 3H), 3.93 (s, 3H), 4.05 (d, 1H, J=9.5 Hz), 8.15 (s, 1H), 9.56(s, 1H).

I-144

mp: 177-178° C. ¹H-NMR (CDCl₃) δ ppm: 1.27-1.39 (m, 2H), 1.40 (s, 9H),1.65-1.79 (m, 2H), 2.04-2.07 (m, 2H), 2.12-2.34 (m, 3H), 3.22 (m, 1H),3.93 (d, 1H, J=9.1 Hz), 6.90-7.03 (m, 3H), 7.25 (m, 1H), 7.77 (dd, 1H,J=4.9, 1.7 Hz), 7.81 (brs, 1H), 8.72 (dd, 1H, J=7.8, 1.5 Hz).

I-145

mp:>300° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.30 (s, 9H), 1.44-1.70 (m, 4H),2.05-2.19 (m, 4H), 2.73 (m, 1H), 3.18 (m, 1H), 6.86 (d, 1H, J=8.8 Hz),7.62 (t, 2H, J=8.5 Hz), 7.86 (t, 2H, J=8.5 Hz), 7.89 (d, 2H, J=8.5 Hz),8.16 (d, 2H, J=8.5 Hz).

I-146

mp: 240-242° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.26-1.53 (m, 4H), 1.27 (s, 9H),1.74-1.83 (m, 2H), 1.90-1.97 (m, 2H), 2.26 (m, 1H), 3.04 (m, 1H), 6.59(brs, 1H), 6.74-6.79 (m, 3H), 7.74 (s, 1H), 10.32 (s, 1H), 12.80 (s,1H).

I-147

mp: 167-169° C. ¹H-NMR (CDCl₃) δ ppm: 1.05-1.28 (m, 2H), 1.38 (s, 9H),1.47-1.70 (m, 2H), 1.80-2.00 (m, 3H), 2.13-2.25 (m, 2H), 2.75 (t, 2H,J=6.9 Hz), 3.24 (m, 1H), 3.49 (dt, 2H, J=6.3, 6.9 Hz), 3.58 (d, 1H,J=8.7 Hz), 3.87 (s, 6H), 5.40 (brs, 1H), 6.71 (m, 2H), 6.82 (d, 1H,J=8.7 Hz).

I-148

mp: 171-172° C. ¹H-NMR (CDCl₃) δ ppm: 1.16-1.38 (m, 2H), 1.39 (s, 9H),1.50-1.79 (m, 4H), 1.85-2.02 (m, 3H), 2.15-2.30 (m, 2H), 2.35-2.56 (m,6H), 3.25 (m, 1H), 3.33 (q, 2H, J=6.0 Hz), 3.63 (d, 1H, J=9.0 Hz), 3.72(t, 4H, J=4.6 Hz), 6.77 (brs, 1H).

I-149

¹H-NMR (CDCl₃) δ ppm: 1.20-1.36 (m, 2H), 1.28 (t, 3H, J=7.2 Hz), 1.39(s, 9H), 1.45-1.70 (m, 2H), 1.85-2.30 (m, 7H), 2.43 (s, 3H), 3.05-3.42(m, 3H), 3.46-3.80 (m, 3H), 7.31 (d, 1H, J=7.2 Hz), 7.40-7.52 (m, 3H),8.18 (brs, 1H).

I-150

mp: 203-204° C. ¹H-NMR (CDCl₃) δ ppm: 1.15-1.37 (m, 2H), 1.39 (s, 9H),1.42-1.70 (m, 2H), 1.85-2.29 (m, 5H), 2.76 (t, 2H, J=6.0 Hz), 3.26 (m,1H), 3.49 (q, 2H, J=6.0 Hz), 3.61 (m, 1H), 4.03 (s, 2H), 5.88 (brs, 1H),7.15 (dd, 1H, J=7.0, 8.8 Hz), 7.30-7.35 (m, 2H).

I-151

mp: 181-183° C. ¹H-NMR (CDCl₃) δ ppm: 1.15-1.30 (m, 2H), 1.39 (s, 9H),1.45-1.64 (m, 2H), 1.88-2.05 (m, 3H), 2.15-2.25 (m, 2H), 2.69 (t, 2H,J=6.0 Hz), 3.28 (m, 1H), 3.47 (q, 2H, J=6.0 Hz), 3.58 (d, 1H, J=9.9 Hz),3.87 (s, 2H), 5.83 (brs, 1H), 7.00 (m, 1H), 7.20 (m, 2H).

I-152

mp: 222-224° C. ¹H-NMR (CDCl₃) δ ppm: 1.16-1.37 (m, 2H), 1.39 (s, 9H),1.49-1.70 (m, 2H), 1.90-2.25 (m, 5H), 3.26 (m, 1H), 3.36 (t, 2H, J=6.4Hz), 3.66 (dt, 3H, J=6.0, 6.4 Hz), 5.87 (t, 1H, J=6.0 Hz), 7.58 (s, 1H),7.68 (dd, 1H, J=7.0, 8.5 Hz), 7.83 (dd, 1H, J=7.0, 8.5 Hz), 8.19 (t, 2H,J=8.5 Hz).

I-153

mp: 207-209° C. ¹H-NMR (CDCl₃) δ ppm: 1.05-1.25 (m, 2H), 1.38 (s, 9H),1.40-2.03 (m, 10H), 2.05-2.25 (m, 2H), 2.58 (s, 3H), 2.76 (m, 1H),3.05-3.35 (m, 2H), 3.97 (d, 1H, J=9.5 Hz), 4.94 (t, 1H, J=4.0 Hz), 8.42(d, 1H, J=5.5 Hz), 8.97 (d, 1H, J=5.5 Hz).

I-154

mp: 184-185° C. ¹H-NMR (CDCl₃) δ ppm: 1.05-1.25 (m, 2H), 1.37 (s, 9H),1.50-1.69 (m, 2H), 1.85-2.05 (m, 3H), 2.10-2.21 (m, 2H), 3.24 (m, 1H),3.64 (m, 1H), 4.87 (s, 1H), 4.88 (s, 1H), 5.67 (brs, 1H), 7.42 (d, 2H,J=5.5 Hz), 7.52 (m, 2H), 7.78 (m, 1H), 7.82 (m, 1H), 7.95 (d, 1H, J=7.0Hz).

I-155

mp: 208-210° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.26 (s, 9H), 1.27-1.50 (m, 4H),1.75-2.00 (m, 4H), 2.16 (m, 1H), 2.81 (s, 3H), 3.02 (m, 1H), 6.79 (d,1H, J=8.5 Hz), 10.00 (s, 1H), 10.66 (s, 1H).

I-156

mp: 256-257° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.39 (m, 2H), 1.41 (s, 9H),1.60-1.81 (m, 2H), 2.01-2.35 (m, 5H), 2.69 (t, 2H, J=6.0 Hz), 3.11 (t,2H, J=6.0 Hz), 3.30 (m, 1H), 3.61 (d, 1H, J=9.3 Hz), 7.21 (d, 1H, J=8.0Hz), 7.31 (s, 1H), 7.70 (d, 1H, J=8.0 Hz), 7.99 (s, 1H).

I-157

mp: 269-271° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.45 (m, 2H), 1.41 (s, 9H),1.70-1.90 (m, 2H), 2.10-2.45 (m, 5H), 3.37 (m, 1H), 3.68 (m, 1H), 7.45(dd, 1H, J=4.0, 8.0 Hz), 7.53 (brs, 1H), 7.72 (t, 1H, J=8.0 Hz), 7.83(d, 1H, J=8.0 Hz), 8.02 (d, 1H, J=8.0 Hz), 8.18 (d, 1H, J=8.0 Hz), 8.93(d, 1H, J=4.0 Hz).

I-158

mp: 253-255° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.40 (m, 2H), 1.42 (s, 9H),1.60-1.90 (m, 2H), 2.06-2.50 (m, 5H), 2.72 (s, 3H), 3.33 (m, 1H), 3.78(d, 1H, J=9.2 Hz), 7.52 (t, 1H, J=7.0 Hz), 7.62-7.80 (m, 2H), 7.94 (brs,1H), 8.05 (d, 1H, J=8.5 Hz), 8.20 (s, 1H).

I-159

mp: 253-255° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.39 (m, 2H), 1.40 (s, 9H),1.60-1.80 (m, 2H), 1.98-2.30 (m, 5H), 2.71 (s, 3H), 3.31 (m, 1H), 3.68(d, 1H, J=9.0 Hz), 7.41 (brs, 1H), 7.61 (d, 2H, J=9.0 Hz), 7.70 (d, 2H,J=9.0 Hz).

I-160

mp: 211-212° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.32 (m, 2H), 1.39 (t, 3H,J=7.0 Hz), 1.40 (s, 9H), 1.55-1.79 (m, 2H), 1.98-2.35 (m, 5H), 3.31 (m,1H), 3.65 (d, 1H, J=9.5 Hz), 4.03 (q, 2H, J=7.0 Hz), 6.64 (d, 1H, J=8.0Hz), 6.92 (d, 1H, J=8.0 Hz), 7.10 (s, 1H), 7.19 (t, 1H, J=8.0 Hz), 7.30(brs, 1H).

I-161

mp: 202-203° C. ¹H-NMR (CDCl₃) δ ppm: 0.96 (t, 1H, J=7.3 Hz), 1.29-1.39(m, 2H), 1.40 (s, 9H), 1.41-1.58 (m, 2H), 1.60-1.80 (m, 4H), 1.98-2.31(m, 5H), 3.31 (m, 1H), 3.66 (d, 1H, J=8.5 Hz), 3.96 (t, 2H, J=6.4 Hz),6.64 (d, 1H, J=8.0 Hz), 6.90 (d, 1H, J=8.0 Hz), 7.11 (s, 1H), 7.19 (t,1H, J=8.0 Hz), 7.31 (brs, 1H).

I-162

mp: 177-180° C. ¹H-NMR (CDCl₃) δ ppm: 1.18-1.38 (m, 2H), 1.39 (s, 9H),1.59-1.78 (m, 2H), 1.95-2.05 (m, 2H), 2.07-2.25 (m, 3H), 3.26 (m, 1H),3.46 (s, 3H), 4.17 (d, 1H, J=9.5 Hz), 5.15 (s, 2H), 6.77 (d, 1H, J=8.0Hz), 7.10-7.23 (m, 2H), 7.34 (s, 1H), 7.58 (s, 1H).

I-163

mp: 175-178° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.28-1.50 (m, 4H),1.78-2.00 (m, 4H), 2.22 (m, 1H), 2.96-3.15 (m, 2H), 6.67 (m, 1H), 6.79(d, 1H, J=8.5 Hz), 7.18 (m, 2H), 7.38 (s, 1H), 9.81 (s, 1H).

I-164

mp: 232-233° C. ¹H-NMR (CDCl₃) δ ppm: 0.97 (t, 3H, J=7.3 Hz), 1.22-1.30(m, 2H), 1.40 (s, 9H), 1.44-1.51 (m, 2H), 1.67-1.77 (m, 4H), 2.02-2.24(m, 5H), 3.22 (m, 1H), 3.62 (d, 1H, J=9.6 Hz), 4.25 (t, 2H, J=6.8 Hz),6.71 (d, 1H, J=8.4 Hz), 7.01 (brs, 1H), 7.91 (dd, 1H, J=8.4, 3.3 Hz),8.08 (d, 1H, J=3.3 Hz).

I-165

mp: 199-200° C. ¹H-NMR (CDCl₃) δ ppm: 0.96 (t, 3H, J=7.4 Hz), 1.24-1.50(m, 4H), 1.40 (s, 9H), 1.67-1.76 (m, 3H), 2.03-2.08 (m, 2H), 2.24-2.35(m, 3H), 3.29 (m, 1H), 3.76 (d, 1H, J=9.1 Hz), 3.91 (t, 2H, J=6.6 Hz),6.41 (dd, 1H, J=8.8, 2.5 Hz), 6.55 (d, 1H, J=2.5 Hz), 6.82 (d, 1H, J=8.8Hz), 7.43 (s, 1H), 8.95 (s, 1H).

I-166

mp: 215-218° C. ¹H-NMR (CDCl₃+CD₃OD) δ ppm: 0.97 (t, 3H, J=7.4 Hz),1.24-1.40 (m, 4H), 1.39 (s, 9H), 1.42-1.50 (m, 2H), 1.54-1.72 (m, 2H),1.76-1.82 (m, 2H), 1.91-2.00 (m, 2H), 2.06-2.22 (m, 3H), 3.24 (m, 1H),4.00 (t, 2H, J=6.6 Hz), 6.78 (d, 1H, J=8.8 Hz), 6.98 (dd, 1H, J=8.8, 2.5Hz), 7.09 (d, 1H, J=8.8 Hz).

I-167

mp: 212-213° C. ¹H-NMR (CDCl₃) δ ppm: 0.96 (t, 3H, J=7.5 Hz), 1.26-1.34(m, 2H), 1.40 (s, 9H), 1.45-1.50 (m, 2H), 1.68-1.77 (m, 4H), 2.03-2.08(m, 2H), 2.17 (m, 1H), 2.26-2.29 (m, 2H), 3.29 (m, 1H), 3.60 (d, 1H,J=9.0 Hz), 4.25 (t, 2H, J=6.8 Hz), 6.71 (d, 1H, J=8.4 Hz), 7.01 (brs,1H), 7.91 (dd, 1H, J=8.4, 3.3 Hz), 8.08 (d, 1H, J=3.3 Hz).

I-168

mp: 230-232° C. ¹H-NMR (CDCl₃) δ ppm: 1.22-1.35 (m, 2H), 1.40 (s, 9H),1.63-1.77 (m, 2H), 2.03-2.08 (m, 2H), 2.15-2.29 (m, 3H), 3.31 (m, 1H),3.63 (d, 1H, J=9.3 Hz), 6.89 (d, 1H, J=9.4 Hz), 7.10 (brd, 2H, J=7.4Hz), 7.12 (brs, 1H), 7.18 (t, 1H, J=7.4 Hz), 7.36 (brt, 2H, J=7.4 Hz),8.09-8.15 (m, 2H).

I-169

mp: 159-160° C. ¹H-NMR (CDCl₃) δ ppm: 0.97 (t, 3H, J=7.3), 1.20-1.35 (m,2H), 1.40 (s, 9H), 1.37-1.49 (m, 2H), 1.61-1.78 (m, 4H), 2.05-2.08 (m,2H), 2.23-2.26 (m, 2H), 2.36 (s, 3H), 2.97 (brs, 1H), 3.32 (m, 1H), 3.86(brs, 1H), 4.30 (t, 2H, J=6.5 Hz), 6.25 (s, 1H), 7.92 (brs, 1H).

I-170

mp: 180-181° C. ¹H-NMR (CDCl₃) δ ppm: 0.88-0.89 (m, 2H), 1.39 (s, 9H),1.42-1.60 (m, 2H), 1.86-1.90 (m, 2H), 2.04-2.09 (m, 2H), 2.42 (s, 3H),2.91 (m, 1H), 3.20 (m, 1H), 3.63 (d, 1H, J=9.2 Hz), 6.38 (s, 1H), 7.15(m, 2H), 7.28 (m, 1H), 7.45 (m, 2H), 7.84 (brs, 1H).

I-171

mp: 173-174° C. ¹H-NMR (CDCl₃) δ ppm: 0.98 (t, 3H, J=7.5 Hz), 1.29-1.40(m, 2H), 1.40 (s, 9H), 1.55 (m, 2H), 1.62-1.83 (m, 4H), 2.09-2.12 (m,2H), 2.24-2.32 (m, 3H), 3.32 (m, 1H), 3.63 (d, 1H, J=9.5 Hz), 3.99 (t,2H, J=6.4 Hz), 7.22 (dd, 1H, J=9.4, 2.7 Hz), 7.66 (d, 1H, J=2.7 Hz),8.63 (d, 1H, J=9.4 Hz), 10.17 (s, 1H).

I-172

mp: 238-242° C. ¹H-NMR (CDCl₃) δ ppm: 0.96 (t, 3H, J=7.3 Hz), 1.23-1.52(m, 4H), 1.40 (s, 9H), 1.61-1.78 (m, 4H), 2.05-2.28 (m, 5H), 3.30 (m,1H), 3.66 (d, 1H, J=9.4 Hz), 3.84 (brs, 2H), 3.90 (t, 2H, J=6.4 Hz),6.32-6.35 (m, 2H), 6.96 (brs, 1H), 6.97 (d, 1H, J=9.4 Hz).

I-173

mp: 165-166° C. ¹H-NMR (CDCl₃) δ ppm: 1.23-1.26 (m, 2H), 1.40 (s, 9H),1.67-1.72 (m, 2H), 2.01-2.06 (m, 2H), 2.11-2.28 (m, 3H), 3.31 (m, 1H),3.60 (s, 2H), 3.69 (s, 3H), 4.02 (brs, 1H), 7.01 (d, 1H, J=8.0 Hz), 7.25(t, 1H, J=8.0 Hz), 7.43 (d, 1H, J=8.0 Hz), 7.49 (brs, 1H), 7.51 (brs,1H).

I-174

mp: 264-265° C. ¹H-NMR (CDCl₃+CD₃OD) δ ppm: 1.26-1.29 (m, 2H), 1.39 (s,9H), 1.62-1.69 (m, 2H), 1.96-2.00 (m, 2H), 2.18-2.21 (m, 3H), 3.25 (m,1H), 3.58 (s, 2H), 7.01 (d, 1H, J=7.5 Hz), 7.26 (t, 1H, J=7.5 Hz), 7.42(brs, 1H), 7.50 (d, 1H, J=7.5 Hz).

I-175

mp: 90-94° C. ¹H-NMR (CDCl₃) δ ppm: 1.16-1.23 (m, 2H), 1.37 (s, 9H),1.44-1.56 (m, 2H), 1.73-1.85 (m, 3H), 2.11-2.15 (m, 2H), 3.57 (t, 2H,J=6.4 Hz), 3.21 (m, 1H), 3.58 (m, 2H), 3.84 (d, 1H, J=9.3 Hz), 5.56(brs, 1H), 7.01 (s, 1H), 7.11 (t, 1H, J=7.5 Hz), 7.21 (t, 1H, J=7.5 Hz),7.38 (d, 1H, J=7.5 Hz), 7.59 (d, 1H, J=7.5 Hz), 8.24 (brs, 1H).

I-176

mp: 116-118° C. ¹H-NMR (CDCl₃) δ ppm: 1.18-1.38 (m, 2H), 1.40 (s, 9H),1.60-1.79 (m, 2H), 1.95-2.30 (m, 5H), 3.30 (m, 1H), 3.69 (m, 1H), 3.80(s, 3H), 4.64 (s, 2H), 6.67 (d, 1H, J=8.0 Hz), 7.00 (d, 1H, J=8.5 Hz),7.15-7.24 (m, 2H), 7.32 (brs, 1H).

I-177

mp: 219-220° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.28-1.50 (m, 4H),1.75-2.01 (m, 4H), 2.18-2.30 (m, 1H), 2.95-3.15 (m, 2H), 4.61 (s, 2H),6.56 (m, 1H), 6.80 (d, 1H, J=8.5 Hz), 7.16 (m, 2H), 7.28 (brs, 1H), 9.87(brs, 1H).

I-178

mp: 170-173° C. ¹H-NMR (CDCl₃) δ ppm: 1.18-1.39 (m, 2H), 1.40 (s, 9H),1.50-1.80 (m, 2H), 1.90-2.33 (m, 5H), 2.36 (s, 6H), 2.75 (t, 2H, J=5.5Hz), 3.30 (m, 1H), 3.70 (m, 1H), 4.08 (t, 2H, J=5.5 Hz), 6.68 (d, 1H,J=8.0 Hz), 6.94 (d, 1H, J=7.5 Hz), 7.15-7.23 (m, 2H), 7.33 (brs, 1H).

I-179

mp: 191-193° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.39 (m, 2H), 1.40 (s, 9H),1.58-1.80 (m, 2H), 1.98-2.32 (m, 5H), 3.30 (m, 1H), 3.70 (d, 1H, J=9.5Hz), 4.77 (s, 2H), 6.73 (d, 1H, J=8.0 Hz), 7.04 (d, 1H, J=8.0 Hz),7.20-7.31 (m, 2H), 7.48 (brs, 1H).

I-180

mp: 174-176° C. ¹H-NMR (CDCl₃) δ ppm: 1.10-1.30 (m, 2H), 1.40 (s, 9H),1.45-1.65 (m, 2H), 1.81-2.02 (m, 3H), 2.15-2.30 (m, 2H), 2.58 (t, 2H,J=6.5 Hz), 3.25 (m, 1H), 3.37 (dt, 2H, J=5.5, 6.5 Hz), 3.60 (d, 1H,J=9.5 Hz), 3.71 (s, 2H), 5.73 (brs, 1H), 7.20-7.40 (m, 5H).

I-181

mp: 176-178° C. ¹H-NMR (CDCl₃) δ ppm: 1.15-1.30 (m, 2H), 1.39 (s, 9H),1.45-1.70 (m, 6H), 1.85-2.01 (m, 3H), 2.15-2.28 (m, 2H), 2.63 (t, 2H,J=7.0 Hz), 3.25 (dt, 2H, J=6.0, 7.0 Hz), 3.27 (m, 1H), 3.63 (m, 1H),5.35 (brs, 1H), 7.17 (m, 3H), 7.29 (m, 2H).

I-182

mp: 152-154° C. ¹H-NMR (CDCl₃) δ ppm: 1.15-1.30 (m, 2H), 1.39 (s, 9H),1.45-1.65 (m, 2H), 1.85-2.05 (m, 3H), 2.09-2.25 (m, 2H), 3.25 (m, 1H),3.45 (dt, 2H, J=5.0, 5.0 Hz), 3.55 (t, 2H, J=5.0 Hz), 3.60 (m, 1H), 4.51(s, 2H), 5.81 (brs, 1H), 7.29-7.40 (m, 5H).

I-183

mp: 208-211° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.31 (m, 2H), 1.39 (s, 9H),1.62-1.68 (m, 2H), 1.98-2.25 (m, 5H), 3.30 (m, 1H), 3.57 (d, 1H, J=9.2Hz), 4.59 (d, 2H, J=5.8 Hz), 5.76 (brs, 1H), 7.37 (dd, 1H, J=8.4, 2.0Hz), 7.46-7.52 (m, 2H), 7.69 (brs, 1H), 7.78-7.83 (m, 3H).

I-184

mp: 180-182° C. ¹H-NMR (CDCl₃) δ ppm: 1.22-1.37 (m, 2H), 1.40 (s, 9H),1.60-1.69 (m, 2H), 2.05-2.09 (m, 2H), 2.21-2.27 (m, 3H), 3.45 (m, 1H),3.64 (d, 1H, J=9.6 Hz), 4.77 (d, 2H, J=4.9 Hz), 7.43 (d, 1H, J=8.6 Hz),7.46 (brs, 1H), 7.61 (t, 1H, J=7.7 Hz), 7.73 (t, 1H, J=7.7 Hz), 7.87 (t,1H, J=7.7 Hz), 8.20 (t, 1H, J=7.7 Hz), 8.24 (d, 1H, J=8.6 Hz).

I-185

mp: 260-261° C. ¹H-NMR (CDCl₃) δ ppm: 1.22-1.32 (m, 2H), 1.39 (s, 9H),1.60-1.70 (m, 2H), 1.97-2.01 (m, 2H), 2.11 (m, 1H), 2.21-2.24 (m, 2H),3.30 (m, 1H), 3.61 (d, 1H, J=9.3 Hz), 4.95 (d, 2H, J=6.0 Hz), 5.85 (brs,1H), 7.33 (d, 1H, J=4.8 Hz), 7.62 (dd, 1H, J=8.4, 6.9 Hz), 7.75 (dd, 1H,J=8.1, 6.9 Hz), 8.00 (d, 1H, J=8.1 Hz), 8.20 (d, 1H, J=8.4 Hz), 8.42 (d,1H, J=4.8 Hz).

I-186

mp: 231-233° C. ¹H-NMR (CDCl₃) δ ppm: 1.23-1.40 (m, 2H), 1.40 (s, 9H),1.62-1.76 (m, 2H), 2.04-2.10 (m, 2H), 2.22-2.32 (m, 3H), 3.30 (m, 1H),3.95 (d, 1H, J=9.3 Hz), 5.04 (d, 2H, J=4.1 Hz), 7.61 (d, 1H, J=5.8 Hz),7.63 (brs, 1H), 7.65 (dd, 1H, J=8.2, 6.9 Hz), 7.73 (dd, 1H, J=8.5, 6.9Hz), 7.86 (d, 1H, J=8.2 Hz), 8.10 (d, 1H, J=8.5 Hz), 8.42 (d, 1H, J=5.8Hz).

I-187

mp: 184-187° C. ¹H-NMR (CDCl₃) δ ppm: 0.97 (t, 3H, J=7.3 Hz), 1.18-1.30(m, 2H), 1.39 (s, 9H), 1.42-1.65 (m, 4H), 1.70-1.80 (m, 2H), 1.94-2.08(m, 3H), 2.18-2.26 (m, 2H), 3.29 (m, 1H), 3.61 (d, 1H, J=9.5 Hz), 3.93(t, 2H, J=6.4 Hz), 4.39 (d, 2H, J=5.5 Hz), 5.67 (brs, 1H), 6.79-6.83 (m,3H), 7.23 (t, 1H, J=7.6 Hz).

I-188

mp: 224-226° C. ¹H-NMR (CDCl₃) δ ppm: 0.16-1.31 (m, 2H), 1.38 (s, 9H),1.55-1.70 (m, 2H), 1.92-2.07 (m, 3H), 2.17-2.23 (m, 2H), 3.21 (m, 1H),3.81 (s, 3H), 3.83 (s, 6H), 4.05 (d, 1H, J=9.8 Hz), 4.34 (d, 2H, J=5.8Hz), 5.96 (brs, 1H), 6.47 (s, 2H).

I-189

mp: 217-218° C. ¹H-NMR (CDCl₃) δ ppm: 1.15-1.30 (m, 2H), 1.37 (s, 9H),1.52-1.66 (m, 2H), 1.90-2.06 (m, 3H), 2.13-2.20 (m, 2H), 2.93 (s, 6H),3.24 (m, 1H), 3.94 (d, 1H, J=9.5 Hz), 4.30 (d, 2H, J=5.5 Hz), 5.73 (brs,1H), 6.69 (d, 2H, J=8.9 Hz), 7.12 (d, 2H, J=8.9 Hz).

I-190

mp: amorphous solid ¹H-NMR (CDCl₃) δ ppm: 1.17-1.32 (m, 2H), 1.39 (s,9H), 1.54-1.72 (m, 2H), 1.96-2.13 (m, 3H), 2.18-2.27 (m, 2H), 3.30 (m,1H), 3.63 (d, 1H, J=9.2 Hz), 4.51 (d, 2H, J=5.8 Hz), 5.82 (brs, 1H),7.40 (d, 2H, J=8.5 Hz), 8.02 (d, 2H, J=8.5 Hz), 8.64 (s, 1H).

I-191

mp: 126-128° C. ¹H-NMR (CDCl₃) δ ppm: 0.97 (t, 3H, J=7.4 Hz), 1.10-1.28(m, 2H), 1.36 (s, 9H), 1.42-1.86 (m, 9H), 2.06-2.18 (m, 2H), 3.22 (m,1H), 3.95 (t, 2H, J=4.5 Hz), 4.16 (brs, 1H), 4.85 (s, 2H), 6.82-6.95 (m,3H), 7.26 (t, 1H, J=7.8 Hz), 8.54 (brs, 1H).

I-192

mp: 178-181° C. ¹H-NMR (CDCl₃) δ ppm: 0.96 (t, 3H, J=7.3 Hz), 1.18-1.52(m, 4H), 1.39 (s, 9H), 1.58-1.76 (m, 4H), 1.92-2.00 (m, 2H), 2.02-2.29(m, 3H), 3.28 (m, 1H), 3.78 (d, 1H, J=9.5 Hz), 3.89 (t, 2H, J=6.6 Hz),6.00 (brs, 1H), 6.78 (s, 4H), 7.35 (brs, 1H).

I-193

mp: 187-188° C. ¹H-NMR (CDCl₃+CD₃OD) δ ppm: 1.21-1.40 (m, 2H), 1.38 (s,9H), 1.52-1.69 (m, 2H), 1.90-2.00 (m, 2H), 2.02-2.20 (m, 3H), 3.22 (m,1H), 3.75 (s, 3H), 6.79 (s, 4H).

I-194

mp: 251-253° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.24-1.50 (m, 4H),1.72-1.83 (m, 2H), 1.91-1.99 (m, 2H), 2.16 (m, 1H), 3.02 (m, 1H), 3.82(s, 3H), 6.79 (d, 1H, J=8.2 Hz), 7.01 (d, 2H, J=8.8 Hz), 7.85 (d, 2H,J=8.8 Hz), 9.72 (brs, 1H), 8.64 (brs, 1H).

I-195

mp: 183-185° C. ¹H-NMR (CDCl₃) δ ppm: 1.22-1.37 (m, 2H), 1.40 (s, 9H),1.58-1.75 (m, 2H), 2.05-2.10 (m, 2H), 2.20-2.30 (m, 3H), 3.32 (m, 1H),3.70 (s, 2H), 3.73 (s, 3H), 6.79 (s, 1H), 8.83 (brs, 1H).

I-196

mp: 185-187° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.39 (m, 2H), 1.40 (s, 9H),1.44 (t, 6H, J=7.0 Hz), 1.60-1.80 (m, 2H), 1.95-2.35 (m, 5H), 3.30 (m,1H), 3.62 (d, 1H, J=8.9 Hz), 4.06 (q, 2H, J=7.0 Hz), 4.09 (q, 2H, J=7.0Hz), 6.08 (s, 1H), 7.02 (s, 1H), 7.36 (s, 1H).

I-197

mp: 211-213° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.40 (m, 2H), 1.41 (s, 9H),1.60-1.80 (m, 2H), 2.00-2.36 (m, 5H), 2.61 (s, 3H), 3.32 (m, 1H), 3.64(d, 1H, J=9.2 Hz), 7.28 (s, 1H), 7.43 (t, 1H, J=7.5 Hz), 7.69 (d, 1H,J=7.5 Hz), 7.85 (d, 1H, J=7.5 Hz), 8.02 (s, 1H).

I-198

mp: 268-269° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.39 (m, 2H), 1.40 (s, 9H),1.42-2.32 (m, 7H), 2.90-3.10 (m, 4H), 3.30 (m, 1H), 3.68 (d, 1H, J=8.8Hz), 6.59 (s, 1H), 7.18 (d, 1H, J=8.7 Hz), 7.59 (d, 1H, J=8.7 Hz), 7.77(brs, 1H).

I-199 mp: 221-224° C.

I-200 mp: 237-240° C.

I-201 mp: 87-90° C.

I-202 mp: 222-223° C.

I-203 mp: 255-257° C.

I-204 mp: 234-236° C.

I-205 mp: 208-210° C.

I-206 mp: 217-218° C.

I-207 mp: 275-279° C.

I-208 mp: 248-250° C.

I-209 mp: 256-258° C.

I-210 mp: 270-271° C.

I-211 mp: 219-220° C.

I-212 mp: 260-261° C.

I-213 mp:>300° C.

I-214 mp: 206-207° C.

¹H-NMR (CDCl₃) δ ppm: 0.93 (t, 3H, J=7.4 Hz), 1.30-1.42 (m, 2H), 1.49(d, 6H, J=6.9 Hz), 1.53-1.65 (m, 2H), 2.61 (t, 2H, J=7.7 Hz), 4.15(sept, 1H, J=6.9 Hz), 7.04 (d, 1H, J=8.2 Hz), 7.20 (d, 2H, J=8.2 Hz),7.51 (d, 2H, J=8.2 Hz), 7.89 (d, 1H, J=8.8 Hz), 8.18 (s, 1H, 10.55 (s,1H).

I-215

¹H-NMR (CDCl₃) δ ppm: 0.93 (t, 3H, J=7.3 Hz), 1.30-1.41 (m, 2H),1.52-1.63 (m, 2H), 1.95 (s, 6H), 2.61 (t, 2H, J=7.8 Hz), 6.99 (brs, 1H),7.20 (d, 2H, J=8.5 Hz), 7.65 (d, 2H, J=8.5 Hz), 7.9:3 (dd, 1H, J=8.5,2.5 Hz), 8.28 (d, 1H, J=8.5 Hz), 8.55 (d, 1H, J=2.5 Hz), 9.76 (brs, 1H).

Ia-1

mp 221-224° C. ¹H-NMR (CDCl₃) δ ppm: 1.19-1.38 (m, 2H), 1.40 (s, 9H),1.62-1.77 (m, 2H), 2.00-2.31 (m, 5H), 3.18 (t, 4H, J=4.8 Hz), 3.21-3.38(m, 1H), 3.85 (t, 4H, J=4.8 Hz), 6.64-6.32 (m, 2H), 7.11. (s, 1H), 7.20(t, 1H, J=7.8 Hz), 7.45 (s, 1H).

Ia-3

mp 87-90° C. ¹H-NMR (CDCl₃) δ ppm: 1.25 (d, 6H, J=6.3 Hz), 1.37 (d, 6H,J=6.9 Hz), 1.59-1.70 (m, 2H), 1.76-1.88 (m, 2H), 2.32-2.42 (m, 4H),3.11-3.23 (m, 3H), 3.39 (d, 2H, J=10.8 Hz), 3.74-3.86 (m, 2H), 4.34 (t,1H, J=9.0 Hz), 6.86 (d, 2H, J=9.0 Hz), 7.30 (s, 1H), 7.40 (d, 2H, J=9.0Hz).

Ia-4

mp 233-234° C. ¹H-NMR (CDCl₃) δ ppm: 1.25 (d, 6H, J=6.3 Hz), 1.40 (s,9H), 1.26-1.37 (m, 2H), 1.62-1.78 (m, 2H), 2.00-2.22 (m, 5H), 2.42 (t,2H, J=11.7 Hz), 3.20-3.40 (m, 1H), 3.46 (d, 2H, J=10.5 Hz), 3.67 (d, 1H,J=9.3 Hz), 3.72-3.84 (m, 2H), 6.62-6.76 (m, 2H), 7.10 (s, 1H), 7.18 (t,1H, J=7.8 Hz), 7.42 (s, 1H).

Ia-5

mp 125-126° C. ¹H-NMR (CDCl₃) δ ppm: 1.25 (d, 6H, J=6.3 Hz), 1.40 (s,9H), 1.59-1.70 (m, 2H), 1.77-1.84 (m, 2H), 2.30-2.46 (m, 4H), 3.24 (q,2H, J=6.6 Hz), 3.38 (d, 2H, J=11.7 Hz), 3.74-3.88 (m, 2H), 4.08 (t, 1H,J=5.7 Hz), 6.87 (d, 2H, J=8.7 Hz), 7.30 (s, 1H), 7.41 (d, 2H, J=8.7 Hz).

Ia-6

mp 229-230° C. ¹H-NMR (CDCl₃) δ ppm: 1.25 (d, 6H, J=6.3 Hz), 1.26-1.34(m, 2H), 1.39 (d, 6H, J=6.9 Hz), 1.61-1.77 (m, 2H), 1.98-1.26 (m, 5H),2.32-2.46 (m, 2H), 3.15 (quintet, 1H, J=6.6 Hz), 3.22-3.35 (m, 1H), 3.39(d, 2H, J=11.4 Hz), 3.74-3.92 (m, 2H), 3.88 (d, 1H, J=8.4 Hz), 6.96-6.71(m, 2H), 7.05 (brs, 1H), 7.39 (d, 2H, J=9.3 Hz).

Ia-7

mp 253-254° C. ¹H-NMR (DMSO) δ ppm: 1.24-1.60 (m, 4H), 1.27 (s, 9H),1.77-2.07 (m, 4H), 2.16-2.34 (m, 1H), 2.97-3.15 (m, 1H), 6.78 (d, 1H,J=7.2 Hz), 7.01 (t, 1H, J=6.0 Hz), 7.27 (t, 2H, J=6.6 Hz), 7.58 (d, 2H,J=7.5 Hz), 9.78 (s, 1H).

Ia-8

mp 257-258° C. ¹H-NMR (DMSO) δ ppm: 1.22-1.54 (m, 4H), 1.27 (s, 9H),1.77-1.88 (m, 2H), 1.88-2.00 (m, 2H), 2.16-2.34 (m, 1H), 2.23 (s, 3H),2.92-3.14 (m, 1H), 6.77 (d, 1H, J=8.4 Hz), 7.07 (d, 2H, J=8.4 Hz), 7.46(d, 2H, J=8.1 Hz), 9.68 (s, 1H).

Ia-9

mp 231-232° C. ¹H-NMR (CDCl₃) δ ppm: 1.21 (t, 3H, J=7.5 Hz), 1.22-1.38(m, 2H), 1.40 (s, 9H), 1.62-1.78 (m, 2H), 1.98-2.31 (m, 5H), 2.61 (q,2H, J=7.5 Hz), 3.24-3.38 (m, 1H), 3.70 (d, 1H, J=9.9 Hz), 7.11 (s, 1H),7.14 (d, 2H, J=8.7 Hz), 7.40 (d, 2H, J=8.7 Hz).

Ia-10

mp 233-234° C. ¹H-NMR (CDCl₃) δ ppm: 0.96 (t, 3H, J=7.2 Hz), 1.20-1.37(m, 2H), 1.40 (s, 9H), 1.56-1.78 (m, 4H), 1.98-2.32 (m, 5H), 2.54 (t,2H, J=7.2 Hz), 3.23-3.39 (m, 1H), 3.66 (d, 1H, J=9.6 Hz), 7.08 (s, 1H),7.12 (d, 2H, J=8.4 Hz), 7.39 (d, 2H, J=8.4 Hz).

Ia-11

mp 243-244° C. ¹H-NMR (CDCl₃) δ ppm: 1.22 (d, 6H, J=6.9), 1.22-1.77 (m,4H), 1.40 (s, 9H), 2.01-2.30 (m, 5H), 2.83-2.92 (m, 1H), 3.24-3.40 (m,1H), 3.66-3.69 (m, 1H), 7.09 (s, 1H), 7.17 (d, 2H, J=8.4 Hz), 7.41 (d,2H, J=8.1 Hz).

Ia-12

mp 246-247° C.

¹H-NMR (CDCl₃) δ ppm: 0.80 (t, 3H, J=7.5), 1.20 (d, 3H, J=7.2),1.26-1.77 (m, 6H), 1.40 (s, 9H), 2.01-2.27 (m, 5H), 2.51-2.60 (m, 1H),3.20-3.38 (m, 1H), 3.64-3.69 (m, 1H), 7.08 (s, 1H), 7.12 (d, 2H, J=8.4Hz), 7.41 (d, 2H, J=8.4 Hz).

Ia-13

mp 278-279° C. ¹H-NMR (CDCl₃) δ ppm: 1.22-1.52 (m, 4H), 1.29 (s, 9H),1.40 (s, 9H), 1.61-1.77 (m, 2H), 2.02-2.30 (m, 5H), 3.20-3.38 (m, 1H),3.66-3.69 (m, 1H), 7.10 (s, 1H), 7.33 (d, 2H, J=9.0 Hz), 7.42 (d, 2H,J=8.7 Hz).

Ia-14

mp 263-264° C. ¹H-NMR (DMSO) δ ppm: 1.24-1.51 (m, 4H), 1.27 (s, 9H),1.82-1.99 (m, 411), 2.19-2.28 (m, 1H), 2.98-3.12 (m, 1H), 6.78 (d, 1H,J=8.7 Hz), 7.33 (d, 2H, J=8.7 Hz), 7.61 (d, 2H, J=9.0 Hz), 9.94 (s, 1H).

Ia-15

mp 209-210° C. ¹H-NMR (CDCl₃) δ ppm: 1.25 (d, 6H, J=6.3 Hz), 1.40 (s,9H), 1.70-1.98 (m, 8H), 2.19-2.38 (m, 3H), 3.39 (d, 2H, J=11.7 Hz),3.58-3.92 (m, 3H), 4.12-4.26 (m, 1H), 6.82-6.96 (m, 2H), 7.10 (br, 1H),7.41 (d, 2H, J=8.1 Hz).

Ia-16

mp 238-240° C. ¹H-NMR (DMSO) δ ppm: 1.22-1.52 (m, 4H), 1.27 (s, 9H),1.81-1.84 (m, 2H), 1.93-1.97 (m, 2H), 2.16-2.23 (m, 1H), 2.95-3.12 (m,1H), 3.70 (s, 3H), 6.77 (d, 1H; J=8.4 Hz), 6.85 (d, 2H, J=9.0 Hz), 7.48(d, 2H, J=9.3 Hz), 9.64 (s, 1H).

Ia-17

mp 245-246° C. ¹H-NMR (DMSO) δ ppm: 1.22-1.52 (m, 4H), 1.27 (s, 9H),1.83-1.87 (m, 2H), 1.94-1.99 (m, 2H), 2.20-2.28 (m, 1H), 2.98-3.12 (m,1H), 6.78 (d, 1H, J=8.7 Hz), 7.28 (d, 2H, J=8.7 Hz), 7.69 (d, 2H, J=9.0Hz), 9.64 (s, 1H).

Ia-18

mp 240-241° C. ¹H-NMR (CDCl₃) δ ppm: 1.22-1.78 (m, 4H), 1.40 (s, 9H),2.05-2.33 (m, 5H), 3.22-3.44 (m, 1H), 3.64-3.67 (m, 1H), 6.61 (s, 1H),6.69-6.77 (m, 2H).

Ia-19

mp 240-241° C. ¹H-NMR (CDCl₃) δ ppm: 1.24-1.77 (m, 4H), 1.40 (s, 9H),2.05-2.30 (m, 5H), 3.22-3.38 (m, 1H), 3.70-3.74 (m, 1H), 7.00-7.15 (m,3H), 7.36 (s, 1H), 8.29-8.34 (m, 1H).

Ia-20

mp 239-240° C. ¹H-NMR (CDCl₃) δ ppm: 1.24-1.78 (m, 4H), 1.40 (s, 9H),2.02-2.30 (m, 5H), 3.22-3.40 (m, 1H), 3.63-3.66 (m, 1H), 6.89-6.84 (m,1H), 7.10-7.17 (m, 2H), 7.22-7.34 (m, 1H), 7.48-7.51 (m, 1H).

Ia-21

mp 259-260° C. ¹H-NMR (CDCl₃/DMSO) δ ppm: 1.21 (d, 6H, J=6.0 Hz),1.22-1.44 (m, 2H), 1.40 (s, 9H), 1.60-1.78 (m, 2H), 1.87-2.03 (m, 2H),2.08-2.29 (m, 3H), 2.39 (t, 2H, J=10.2 Hz), 3.14-3.32 (m, 1H), 3.19 (d,2H, J=11.4 Hz), 3.77-3.93 (m, 2H), 5.33 (d, 1H, J=9.0 Hz), 6.84 (dd, 1H,JFH, HH=8.1, 8.1 Hz), 7.20 (d, 1H, J=7.8 Hz), 7.49 (d, 1H, JFH=14.7 Hz),8.86 (s, 1H).

Ia-22

mp 234-235° C. ¹H-NMR (CDCl₃) δ ppm: 1.20 (d, 6H, J=5.7 Hz), 1.22-1.44(m, 2H), 1.38 (s, 9H), 1.54-1.76 (m, 2H), 1.94-2.32 (m, 5H), 2.27 (s,3H), 2.39 (t, 2H, J=10.8 Hz), 2.87 (d, 2H, J=11.4 Hz), 3.20-3.40 (m,1H), 3.76-3.92 (m, 2H), 3.91 (d, 1H, J=9.3 Hz), 6.93 (d, 1H, J=8.1 Hz),7.21 (brs, 1H), 7.27 (brs, 1H), 7.36 (brs, 1H).

Ia-23

mp 195-196° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.44 (m, 4H), 1.41 (s, 9H),1.59-1.76 (m, 2H), 2.03-2.14 (m, 2H), 2.15-2.33 (m, 3H), 3.20-3.40 (m,1H), 3.64 (s, 1H, J=9.0 Hz), 7.19-7.24 (m, 1H), 7.44 (brs, 1H),7.52-7.63 (m, 2H), 8.17 (d, 1H, J=8.7 Hz).

Ia-24

mp 209-210° C. ¹H-NMR (CDCl₃) δ ppm: 1.22-1.39 (m, 2H), 1.56 (s, 9H),1.61-1.78 (m, 2H), 2.00-2.12 (m, 2H), 2.17-2.33 (m, 3H), 3.24-3.39 (m,1H), 3.67 (d, 1H, J=9.6 Hz), 6.90-7.01 (m, 1H), 7.21 (s, 1H), 7.95-8.06(m, 1H).

Ia-25

mp 278-281° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.10 (d, 6H, J=6.3 Hz), 1.27 (s,9H), 1.28-1.55 (m, 4H), 1.78-2.00 (m, 4H), 2.11-2.26 (m, 1H), 2.31 (t,2H, J=11.1 Hz), 3.00-3.10 (m, 1H), 3.08 (d, 1H, J=10.8 Hz), 3.67-3.80(m, 2H), 6.78 (d, 1H, J=8.7 Hz), 7.08 (d, 1H, J=9.0 Hz), 7.41 (dd, 1H,J=2.4, 8.7 Hz), 7.78 (d, 1H, J=8.7 Hz), 9.85 (s, 1H).

Ia-26

mp 253-255° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.13 (d, 6H, J=6.0 Hz), 1.27 (s,9H), 1.28-1.52 (m, 4H), 1.78-2.00 (m, 4H), 2.21 (t, 2H, J=11.1 Hz),2.26-2.36 (m, 1H), 2.96-3.10 (m, 1H), 3.56 (d, 1H, J=12.3 Hz), 3.60-3.72(m, 2H), 6.66-6.84 (m, 4H), 7.47 (t, 1H, J=9.3 Hz), 9.28 (s, 1H).

Ia-27

mp 223-226° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.09 (d, 6H, J=6.3 Hz), 1.27 (s,9H), 1.28-1.54 (m, 4H), 1.77-2.01 (m, 4H), 2.32 (t, 2H, J=11.1 Hz),2.32-2.42 (m, 1H), 2.90 (d, 1H, J=11.4 Hz), 2.96-3.12 (m, 1H), 3.76-3.92(m, 2H), 6.78-6.98 (m, 3H), 7.68 (dd, 1H, J=3.3, 8.7 Hz), 8.84 (s, 1H).

Ia-28

mp 237-238° C. ¹H-NMR (CDCl₃) δ ppm: 1.22-1.44 (m, 2H), 1.25 (d, 6H,J=6.3 Hz), 1.40 (s, 9H), 1.61-1.79 (m, 2H), 2.05-2.32 (m, 5H), 2.21 (s,3H), 2.38 (t, 2H, J=10.2 Hz), 3.22-3.42 (m, 1H), 3.40 (d, 2H, J=11.1Hz), 3.65 (d, 1H, J=9.3 Hz), 3.72-3.90 (m, 2H), 6.70-6.78 (m, 2H), 6.81(brs, 1H), 7.50 (d, 1H, J=9.6 Hz).

Ia-29

mp 208-209° C. ¹H-NMR (CDCl₃) δ ppm: 1.22 (d, 6H, J=6.0 Hz), 1.23-1.40(m, 2H), 1.40 (s, 9H), 1.60-1.78 (m, 2H), 2.00-2.16 (m, 2H), 2.14-2.33(m, 3H), 2.45 (t, 2H, J=11.1 Hz), 3.21 (d, 2H, J=10.8 Hz), 3.24-3.38 (m,1H), 3.63 (d, 1H, J=9.3 Hz), 3.80-3.94 (m, 2H), 5.33 (d, 1H, J=9.0 Hz),6.66 (dd, 1H, JFH, HH=6.6, 6.6 Hz), 7.16 (brs, 1H), 7.89 (dd, 1H, JFH,HH=9.0, 9.0 Hz).

Ia-30

mp 284-287° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.08 (d, 6H, J=6.0 Hz), 1.26 (s,9H), 1.28-1.53 (m, 4H), 1.82-2.22 (m, 4H), 2.25-2.39 (m, 1H), 2.78 (t,2H, J=10.5 Hz), 2.97-3.14 (m, 1H), 3.18 (d, 2H, J=11.4 Hz), 3.65-3.76(m, 2H), 6.79 (d, 1H, J=8.7 Hz), 9.75 (s, 1H).

Ia-31

mp 200-201° C. ¹H-NMR (CDCl₃) δ ppm: 1.22-1.40 (m, 2H), 1.40 (s, 9H),1.62-1.76 (m, 2H), 2.04-2.32 (m, 5H), 3.22-3.40 (m, 1H), 3.62-3.66 (m,1H), 7.22-7.24 (m, 1H), 7.38-7.38 (m, 1H), 7.60 (s, 1H), 8.33-8.36 (m,1H).

Ia-32

mp 260-261° C. ¹H-NMR (CDCl₃/DMSO) δ ppm: 1.25-1.42 (m, 2H), 1.38 (s,9H), 1.64 (q, 2H, J=13.5 Hz), 1.95 (d, 2H, J=12.3 Hz), 2.16 (d, 2H,J=10.5 Hz), 2.18-2.32 (m, 1H), 3.14-3.30 (m, 1H), 5.53 (d, 1H, J=9.0Hz), 7.31 (d, 1H, J=8.7 Hz), 7.46 (dd, 1H, J=2.4, 8.7 Hz), 7.90 (d, 1H,J=2.1 Hz), 9.35 (s, 1H).

Ia-33

mp 227° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.30-1.56 (m, 4H),1.78-2.01 (m, 2H), 2.12-2.36 (m, 2H), 2.96-3.13 (m, 1H), 3.70 (s, 3H),3.71 (s, 3H), 6.77 (d, 1H, J=8.7 Hz), 6.85 (d, 1H, J=8.7 Hz), 7.06 (dd,1H, J=2.4, 8.7 Hz), 7.33 (d, 1H, J=2.4 Hz), 9.65 (s, 1H).

Ia-35

mp 214-216° C. ¹H-NMR (CDCl₃) δ ppm: 1.23-1.38 (m, 2H), 1.40 (s, 9H),1.60-1.76 (m, 2H), 2.00-2.12 (m, 2H), 2.20-2.32 (m, 3H), 3.24-3.39 (m,1H), 3.68 (d, 1H, J=9.0 Hz), 6.77 (d, 1H, J=8.7 Hz), 7.00 (dd, 1H,J=2.4, 8.7 Hz), 7.77 (s, 1H), 8.45 (d, 1H, J=2.4 Hz).

Ia-36

mp 241-242° C. ¹H-NMR (CDCl₃/DMSO) δ ppm: 1.25-1.42 (m, 2H), 1.37 (s,9H), 1.62 (q, 2H, J=11.7 Hz), 1.93 (d, 2H, J=12.0 Hz), 2.12 (d, 2H,J=10.8 Hz), 2.16-2.30 (m, 1H), 3.12-3.28 (m, 1H), 3.84 (s, 3H), 6.07 (d,1H, J=8.4 Hz), 6.89 (dd, 1H, JFH, HH=9.3, 9.3 Hz), 7.24 (d, 1H, J=8.7Hz), 7.55 (d, 1H, JFH=13.5 Hz), 9.32 (s, 1H).

Ia-37

mp 248-249° C. ¹H-NMR (CDCl₃) δ ppm: 0.60-0.73 (m, 1H), 0.91 (d, 6H,J=6.6), 1.12-1.40 (m 2H), 1.40 (s, 9H), 1.54-1.88 (m, 5H), 1.98-2.29 (m,7H), 3.22-3.37 (m, 1H), 3.51-3.54 (m, 2H), 3.72 (d, 1H, J=9.6), 6.88 (d,1H, J=8.7), 7.06 (s, 1H), 7.35 (d, 1H, J=9.0).

Ia-38

mp 237-238° C. ¹H-NMR (CDCl₃) δ ppm: 1.01 (d, 6H, J=6.6), 1.20-1.40 (m,2H), 1.40 (s, 9H), 1.60-1.74 (m, 4H), 1.99-2.28 (m, 7H), 2.69-2.82 (m,2H), 3.02-3.14 (m, 2H), 3.20-3.38 (m, 1H), 3.80-3.90 (m, 1H), 6.83-6.86(m, 2H), 7.14 (s, 1H), 7.34 (d, 1H, J=8.4).

Ia-39

mp 234-235° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.36 (m, 2H), 1.40 (s, 9H),1.60-1.77 (m, 2H), 1.90-2.32 (m, 5H), 3.21-3.39 (m, 1H), 3.65 (d, 1H,J=9.6 Hz), 6.87 (d, 1H, J=8.7 Hz), 7.04 (s, 1H), 7.37 (dd, 1H, J=2.7,8.7 Hz), 7.56 (d, 1H, J=2.7 Hz).

Ia-40

mp 257-258° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.14 (d, 6H, J=6.0 Hz), 1.27 (s,9H), 1.28-1.53 (m, 4H), 1.78-2.00 (m, 4H), 2.13-2.256 (m, 1H), 2.30 (t,2H, J=11.7 Hz), 2.97-3.12 (m, 1H), 3.53-3.67 (m, 2H), 4.01 (d, 1H,J=12.3 Hz), 6.80 (dd, 1H, J=3.0, 9.0 Hz), 7.79 (d, 1H, J=9.0 Hz), 8.27(s, 1H), 9.66 (s, 1H).

Ia-41

mp 245-246° C. ¹H-NMR (CDCl₃/DMSO) δ ppm: 1.25-1.42 (m, 2H), 1.37 (s,9H), 1.62 (q, 2H, J=12.6 Hz), 1.94 (d, 2H, J=11.1 Hz), 2.13 (d, 2H,J=11.1 Hz), 2.18-2.35 (m, 1H), 3.11-3.29 (m, 1H), 6.07 (d, 1H, J=8.1Hz), 6.95-7.06 (m, 1H), 7.14-7.27 (m, 1H), 7.44 (d, 1H, J=7.2 Hz), 7.79(s, 1H), 9.48 (s, 1H).

Ia-43

mp 294-295° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.26 (s, 9H), 1.28-1.53 (m, 4H),1.76-1.87 (m, 2H), 1.89-2.00 (m, 2H), 2.13-2.25 (m, 1H), 2.96-3.10 (m,5H), 3.52-3.60 (m, 4H), 6.78 (d, 1H, J=9.0 Hz), 6.88 (d, 2H, J=9.0 Hz),7.44 (d, 2H, J=9.0 Hz), 9.59 (s, 1H).

Ia-44

mp 250-252° C. ¹H-NMR (CDCl₃) δ ppm: 1.13 (d, 6H, J=6.3 Hz), 1.21-1.38(m, 2H), 1.41 (s, 9H), 1.63-1.80 (m, 2H), 1.93 (t, 2H, J=10.8 Hz),2.00-2.10 (m, 2H), 2.16-2.32 (m, 3H), 3.24-3.39 (m, 1H), 3.54 (d, 2H,J=10.2 Hz), 3.64-3.78 (m, 3H), 7.47 (s, 1H), 7.69 (d, 2H, J=9.0 Hz),7.73 (d, 2H, J=9.0 Hz).

Ia-45

mp 193° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.10 (t, 6H, J=7.2 Hz), 1.26 (s, 9H),1.28-1.52 (m, 4H), 1.75-1.86 (m, 2H), 1.89-2.01 (m, 2H), 2.10-2.22 (m,1H), 2.96-3.10 (m, 1H), 3.30-3.52 (m, 12H), 6.60 (d, 2H, J=9.0 Hz), 6.80(d, 1H, J=9.0 Hz), 7.33 (d, 2H, J=9.0 Hz), 9.46 (s, 1H).

Ia-46

mp>300° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.28 (s, 9H), 1.28-1.58 (m, 4H),1.83-2.04 (m, 4H), 2.23-2.36 (m, 1H), 2.46 (s, 3H), 3.00-3.14 (m, 1H),6.79 (d, 1H, J=8.7 Hz), 7.34 (d, 1H, J=8.7 Hz), 7.78 (d, 2H, J=8.7 Hz),7.89 (d, 1H, J=8.4 Hz), 7.91 (s, 1H), 8.00 (d, 2H, J=8.7 Hz), 10.13 (s,1H).

Ia-47

mp 236-237° C. ¹H-NMR (CDCl₃) δ ppm: 0.97 (d, 6H, J=6.6 Hz), 1.01 (d,6H, J=6.6 Hz), 1.20-1.37 (m, 2H), 1.40 (s, 9H), 1.60-1.84 (m, 3H),1.97-2.31 (m, 5H), 2.50 (t, 1H, J=10.8 Hz), 2.78 (dt, 1H, J=3.3, 11.4Hz), 3.25-3.38 (m, 1H), 3.45 (d, 1H, J=11.4 Hz), 3.75 (dt, 1H, J=2.4,11.4 Hz), 4.02 (dt, 1H, J=2.4, 11.4 Hz), 6.88 (d, 2H, J=9.0 Hz), 7.05(s, 1H), 7.39 (d, 2H, J=9.0 Hz).

Ia-48

mp 228-229° C. ¹H-NMR (CDCl₃) δ ppm: 0.88 (t, 6H, J=7.2 Hz), 1.19-1.45(m, 4H), 1.40 (s, 9H), 1.45-1.76 (m, 4H), 1.76-1.92 (m, 1H), 1.96-2.30(m, 5H), 2.66-3.20 (m, 3H), 3.20-3.40 (m, 1H), 3.78 (d, 1H, J=9.3 Hz),3.82 (s, 1H), 6.62-6.98 (m, 2H), 7.09 (brs, 1H), 7.37 (d, 2H, J=7.8 Hz).

Ia-49

mp 262-263° C. ¹H-NMR (CDCl₃/DMSO) δ ppm: 1.21 (d, 6H, J=5.7 Hz),1.26-1.34 (m, 2H), 1.37 (d, 6H), J=5.4 Hz), 1.52-1.76 (m, 2H), 1.85-2.03(m, 2H), 2.03-2.30 (m, 3H), 2.30-2.53 (m, 2H), 3.02-3.33 (m, 4H),3.75-3.98 (m, 2H), 5.70 (brs, 1H), 6.73-6.98 (m, 1H), 7.14-7.25 (m, 1H),7.52 (d, 1H, JFH=13.5 Hz), 8.86 (brs, 1H).

Ia-50

mp 232-233° C. ¹H-NMR (CDCl₃) δ ppm: 1.21 (d, 6H, J=6.3 Hz), 1.22-1.37(m, 2H), 1.38 (d, 6H, J=6.9 Hz), 1.68 (q, 2H, J=12.6 Hz), 1.98-2.26 (m,5H), 2.29 (s, 3H), 2.41 (t, 2H, J=10.2 Hz), 2.88 (d, 2H, J=11.1 Hz),3.15 (septet, 1H, J=6.6 Hz), 3.21-3.37 (m, 1H), 3.77-3.92 (m, 2H), 3.87(d, 1H, J=7.8 Hz), 6.88-7.06 (m, 3H), 7.35 (s, 1H).

Ia-51

mp 211-212° C. ¹H-NMR (CDCl₃) δ ppm: 1.20-1.42 (m, 2H), 1.26 (d, 6H,J=6.3 Hz), 1.38 (d, 6H, J=6.9 Hz), 1.62-1.78 (m, 2H), 1.99-2.28 (m, 5H),2.49 (dd, 2H, J=10.5, 10.5 Hz), 3.17 (quint, 1H, J=6.9 Hz), 3.20-3.38(m, 1H), 3.66-3.99 (m, 2H), 3.90-4.01 (m, 3H), 6.62 (d, 1H, J=9.0 Hz),7.06 (s, 1H), 7.90 (dd, 1H, J=2.4, 9.0 Hz), 8.09 (d, 1H, J=2.4 Hz).

Ia-52

mp 247-249° C. ¹H-NMR (CDCl₃) δ ppm: 1.21-1.36 (m, 2H), 1.40 (s, 9H)1.62-1.78 (m, 2H), 1.98-2.32 (m, 5H), 2.55 (t, 4H, J=6.0 Hz), 3.23-3.38(m, 1H), 3.55 (t, 4H, J=6.0 Hz), 3.72 (d, 1H, J=9.6 Hz), 6.94 (d, 2H,J=9.0 Hz), 7.10 (s, 1H), 7.42 (d, 1H, J=9.0 Hz).

Ia-53

mp 234-235° C. ¹H-NMR (CDCl₃) δ ppm: 1.22-1.38 (m, 2H), 1.41 (s, 9H)1.64-1.80 (m, 2H), 2.00-2.32 (m, 5H), 3.25-3.40 (m, 1H), 3.73 (d, 1H,J=9.3 Hz), 7.43 (s, 1H), 7.48 (t, 2H, J=7.5 Hz), 7.55-7.66 (m, 3H),7.68-7.89 (m, 4H).

Ia-54

mp 235-236° C. ¹H-NMR (CDCl₃) δ ppm: 1.24-1.39 (m, 2H), 1.25 (d, 6H,J=6.3 Hz), 1.39 (d, 6H, J=6.9 Hz), 1.60-1.80 (m, 2H), 2.00-2.28 (m, 5H),2.21 (s, 3H), 2.38 (t, 2H, J=10.8 Hz), 3.15 (septet, 1H, J=6.3 Hz),3.23-3.38 (m, 1H), 3.40 (d, 2H, J=11.7 Hz), 3.72-3.88 (m, 2H), 3.87 (d,1H, J=9.3 Hz), 6.78-6.86 (m, 3H), 7.50 (d, 1H, J=9.6 Hz).

Ia-55

mp 185-186° C. ¹H-NMR (CDCl₃) δ ppm: 1.14 (d, 6H, J=6.3 Hz), 1.22-1.38(m, 2H), 1.41 (s, 9H), 1.62-1.78 (m, 2H), 2.02 (t, 2H, J=10.5 Hz),2.02-2.10 (m, 2H), 2.16-2.31 (m, 3H), 3.24-3.39 (m, 1H), 3.56 (d, 2H,J=9.3 Hz), 3.63-3.80 (m, 3H), 7.46 (dd, 1H, J=1.5, 8.1 Hz), 7.51 (t, 1H,J=8.1 Hz), 7.63 (s, 1H), 7.81 (t, 1H, J=1.8 Hz), 7.98 (dt, 1H, J=1.8,8.1 Hz).

Ia-56

mp 229-230° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.28-1.54 (m, 4H),1.38 (s, 6H), 1.78-1.84 (m, 2H), 1.90-2.00 (m, 2H), 2.15-2.30 (m, 1H),2.97-3.13 (m, 1H), 4.90 (s, 1H), 6.79 (d, 1H, J=9.0 Hz), 7.34 (d, 2H,J=8.7 Hz), 7.48 (d, 2H, J=8.4 Hz), 9.72 (s, 1H).

Ia-57

mp 211-212° C. ¹H-NMR (CDCl₃/DMSO) δ ppm: 1.24-1.40 (m, 2H), 1.38 (s,9H), 1.57-1.74 (m, 2H), 1.91 (s, 3H), 1.92-2.01 (m, 2H), 2.12-2.24 (m,2H), 2.51 (brs, 1H), 3.18-3.33 (m, 1H), 4.96 (d, 1H, J=9.3 Hz),7.16-7.53 (m, 9H), 7.41 (s, 1H).

Ia-58

mp 298-299° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.24 (s, 9H), 1.27 (s, 9H),1.28-1.54 (m, 4H), 1.75-2.02 (m, 4H), 2.14-2.28 (m, 1H), 2.97-3.11 (m,1H), 6.78 (d, 1H, J=8.4 Hz), 7.18 (d, 2H, J=9.0 Hz), 7.48 (d, 2H, J=9.0Hz), 9.46 (s, 1H), 9.76 (s, 1H).

Ia-59

mp 253-254° C. ¹H-NMR (CDCl₃) δ ppm: 1.22-1.40 (m, 2H), 1.41 (s, 9H),1.65-1.81 (m, 2H), 2.04-2.16 (m, 2H), 2.22-2.36 (m, 2H), 3.24-3.41 (m,1H), 3.74 (d, 1H, J=9.6 Hz), 7.40-7.54 (m, 3H), 7.88-8.01 (m, 3H), 8.66(d, 1H, J=1.5 Hz), 9.57 (d, 1H, J=1.2 Hz).

Ia-60

mp 213-214° C. ¹H-NMR (DMSO) δ ppm: 1.32-1.50 (m, 2H), 1.35 (s, 9H),1.52-1.70 (m, 2H), 1.88-2.00 (m, 2H), 2.04-2.16 (m, 2H), 2.22-2.38 (m,1H), 2.65 (s, 3H), 2.99-3.15 (m, 1H), 6.46 (d, 1H, J=9.3 Hz), 7.28 (d,1H, J=9.0 Hz), 7.81 (s, 1H), 8.20 (s, 1H), 8.47 (s, 1H), 9.89 (s, 1H).

Ia-61

mp 274-275° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 1H), 1.28-1.58 (m, 4H),1.84-2.08 (m, 4H), 2.22-2.40 (m, 1H), 2.99-3.15 (m, 1H), 3.01 (s, 3H),6.81 (d, 1H, J=8.1 Hz), 7.78 (d, 2H, J=7.8 Hz), 7.84 (d, 2H, J=8.4 Hz),8.18 (s, 1H), 10.43 (s, 1H).

Ia-62

mp 235-236° C. ¹H-NMR (CDCl₃) δ ppm: 1.22-1.39 (m, 2H), 1.41 (s, 3H),1.66-1.80 (m, 2H), 2.01-2.12 (m, 2H), 2.14-2.22 (m, 1H), 2.23-2.34 (m,2H), 3.24-3.42 (m, 1H), 3.69 (d, 1H, J=9.5 Hz), 6.44 (d, 1H, J=9.3 Hz),7.27 (brs, 1H), 7.28 (d, 1H, J=9.3 Hz), 7.37 (dd, 1H, J=2.4, 9.0 Hz),7.68 (d, 1H, J=9.6 Hz), 8.04 (d, 1H, J=2.4 Hz).

Ia-63

mp 277-279° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.28-1.54 (m, 4H),1.77-2.02 (m, 4H), 2.15-2.29 (m, 1H), 2.90 (s, 3H), 2.96-3.13 (m, 1H),6.79 (d, 1H, J=8.7 Hz), 7.12 (d, 2H, J=9.0 Hz), 7.54 (d, 2H, J=9.0 Hz),9.50 (s, 1H), 9.81 (s, 1H).

Ia-64

mp 259-260° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.26 (s, 9H), 1.26-1.50 (m, 4H),1.74-1.99 (m, 4H), 2.10-2.25 (m, 1H), 2.95-3.10 (m, 1H), 6.78 (d, 1H,J=8.7 Hz), 6.97 (d, 2H, J=9.0 Hz), 7.42 (d, 2H, J=9.0 Hz), 7.50-7.71 (m,5H), 9.73 (s, 1H), 10.05 (s, 1H).

Ia-65

mp 292-293° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.28-1.54 (m, 4H),1.62-1.72 (m, 2H), 1.77-1.87 (m, 2H), 1.91-2.10 (m, 4H), 2.13-2.25 (m,1H), 2.98-3.12 (m, 1H), 3.41-3.52 (m, 2H), 5.09 (s, 1H), 6.79 (d, 1H,J=9.0 Hz), 6.91 (d, 2H, J=9.0 Hz), 7.37 (d, 2H, J=9.0 Hz), 7.42 (d, 2H,J=9.0 Hz), 7.51 (d, 2H, J=9.0 Hz), 9.56 (s, 1H).

Ia-66

mp>300° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.28-1.58 (m, 4H),1.85-2.02 (m, 4H), 2.40-2.52 (m, 1H), 3.00-3.16 (m, 1H), 6.81 (d, 1H,J=9.0 Hz), 7.50-7.58 (m, 3H), 7.90-7.97 (m, 2H), 12.58 (s, 1H).

Ia-67

mp 199-200° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.14 (d, 6H, J=6.3 Hz), 1.28 (s,9H), 1.31-1.48 (m, 4H), 1.76-1.88 (m, 2H), 2.17 (t, 2H, J=11.1 Hz), 2.82(t, 2H, J=11.7 Hz), 3.46 (d, 2H, J=11.4 Hz), 3.20-3.36 (m, 1H),3.62-3.74 (m, 2H), 4.02 (d, 2H, J=12.9 Hz), 6.83 (d, 2H, J=9.0 Hz), 6.89(d, 1H, J=8.7 Hz), 7.28 (d, 2H, J=9.0 Hz), 8.27 (s, 1H).

Ia-68

mp 2:37-239° C. ¹H-NMR (CDCl₃/DMSO) δ ppm: 1.40 (s, 9H), 1.49-1.65 (m,2H), 1.99-2.10 (m, 2H), 1.99-2.10 (m, 2H), 2.95 (t, 2H, J=11.1 Hz),3.36-3.52 (m, 1H), 4.17 (d, 1H, J=12.9 Hz), 5.84 (d, 1H, J=8.7 Hz), 6.39(d, 1H, J=9.6 Hz), 7.21 (d, 1H, J=9.3 Hz), 7.51 (dd, 1H, J=2.4, 9.3 Hz),7.72 (d, 1H, J=9.9 Hz), 7.85 (d, 1H, J=2.7 Hz), 8.04 (s, 1H).

Ia-69

mp 259-260° C. ¹H-NMR (DMSO) δ ppm: 1.25-1.55 (m, 4H), 1.27 (s, 9H),1.82-2.05 (m, 4H), 2.22-2.36 (m, 1H), 2.98-3.17 (m, 1H), 4.16 (s, 3H),6.80 (d, 1H, J=8.4 Hz), 7.77-7.87 (m, 4H), 10.16 (s, 1H).

Ia-70

mp 259-260° C. ¹H-NMR (DMSO) δ ppm: 1.28 (s, 9H), 1.36-1.56 (m, 2H),1.80-1.92 (m, 2H), 2.86-3.02 (m, 2H), 3.36-3.52 (m, 1H), 4.04-4.20 (m,2H), 6.92 (d, 1H, J=7.5 Hz), 7.38-7.58 (m, 3H), 8.00-8.14 (m, 2H), 8.90(s, 1H), 9.08 (s, 1H), 9.63 (s, 1H).

Ia-71

mp 228-229° C. ¹H-NMR (CDCl₃/DMSO) δ ppm: 1.27-1.42 (m, 2H), 1.38 (s,9H), 1.57-1.75 (m, 2H), 1.90-2.02 (m, 2H), 2.12-2.34 (m, 3H), 3.14-3.32(m, 1H), 5.37 (d, 1H, J=9.3 Hz), 7.38-7.43 (m, 3H), 7.46 (d, 2H, J=8.7Hz), 7.51-7.60 (m, 2H), 7.68 (d, 2H, J=9.0 Hz), 9.33 (s, 1H).

Ia-75

mp 169-170° C. ¹H-NMR (CDCl₃) δ ppm: 0.58-0.72 (m, 1H), 0.80 (d, 3H,J=6.6 Hz), 0.94 (d, 3H, J=6.0 Hz), 1.14-1.35 (m, 3H), 1.39 (s, 9H),1.48-1.66 (m, 2H), 1.74-2.06 (m, 5H), 2.06-2.44 (m, 6H), 3.18-3.35 (m,1H), 3.64-3.74 (m, 1H), 4.46-4.60 (m, 1H), 6.98-7.38 (m, 5H).

Ia-76

mp 236-237° C. ¹H-NMR (CDCl₃/DMSO) δ ppm: 1.27-1.42 (m, 2H), 1.38 (d,6H, J=6.6 Hz), 1.60-1.78 (m, 2H), 1.94-2.06 (m, 2H), 2.12-2.30 (m, 3H),3.06-3.34 (m, 2H), 5.10 (brs, 1H), 6.41 (d, 1H, J=9.9 Hz), 7.25 (d, 1H,J=8.4 Hz), 7.48 (dd, 1H, J=2.4, 8.7 Hz), 7.68 (d, 1H, J=9.9 Hz), 8.12(d, 1H, J=2.4 Hz), 8.88 (brs, 1H).

Ia-77

mp 117-118° C. ¹H-NMR (CDCl₃) δ ppm: 1.38 (d, 6H, J=6.9 Hz), 1.65(quintet, 2H, J=5.4 Hz), 1.75-1.91 (m, 2H), 2.42 (t, 2H, J=7.4 Hz),3.10-3.24 (m, 3H), 4.77 (brs, 1H), 6.41 (d, 1H, J=9.6 Hz), 7.18-7.26 (m,1H), 7.48 (dd, 1H, J=1.8, 8.7 Hz), 7.67 (d, 1H, J=9.9 Hz), 8.01 (s, 1H),8.23 (brs, 1H).

Ia-78

mp 138-139° C. ¹H-NMR (CDCl₃) δ ppm: 1.41 (s, 9H), 1.64 (quintet, 2H,J=6.6 Hz), 1.84 (quintet, 2H, J=7.3 Hz), 2.42 (t, 2H, J=7.5 Hz), 3.26(q, 2H, J=6.5 Hz), 4.59 (brs, 1H), 6.41 (d, 1H, J=9.3 Hz), 7.23 (d, 1H,J=8.7 Hz), 7.49 (dd, 1H, J=2.4, 9.0 Hz), 7.67 (d, 1H, J=9.9 Hz), 8.03(d, 1H, J=2.4 Hz), 8.28 (brs, 1H).

Ia-79

mp 289-290° C. ¹H-NMR (DMSO) δ ppm: 1.24-1.63 (m, 4H), 1.28 (s, 9H),1.84-2.08 (m, 4H), 2.24-2.41 (m, 1H), 3.00-3.16 (m, 1H), 6.82 (d, 1H,J=8.1 Hz), 7.36-7.60 (m, 5H), 7.86-7.99 (m, 2H), 8.28 (s, 1H), 10.50 (s,1H).

Ia-80

mp 239-240° C. ¹H-NMR (DMSO) δ ppm: 1.22 (d, 1H, J=6.6 Hz), 1.23-1.40(m, 2H), 1.40-1.59 (m, 2H), 1.83-2.04 (m, 4H), 2.23-2.39 (m, 1H),2.98-3.23 (m, 2H), 7.00 (d, 1H, J=7.8 Hz), 7.36-7,59 (m, 5H), 7.85-7.97(m, 2H), 8.29 (s, 1H), 10.50 (s, 1H).

Ia-81

mp 205-206° C. ¹H-NMR (CDCl₃/DMSO) δ ppm: 1.40 (s, 9H), 1.66 (quintet,2H, J=7.0 Hz), 1.85 (quintet, 2H, J=7.2 Hz), 2.45 (t, 2H, J=7.5 Hz),3.24 (t, 2H, J=6.5 Hz), 5.17 (brs, 1H), 7.36-7.54 (m, 5H), 7.85 (d, 1H,J=8.4 Hz), 8.07 (dd, 1H, J=1.8, 8.1 Hz), 8.23 (d, 1H, J=1.8 Hz), 9.61(s, 1H).

Ia-82

mp 216-217° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.14 (d, 6H, J=6.3 Hz), 1.22 (d,6H, J=6.9 Hz), 1.22-1.53 (m, 4H), 1.76-1.98 (m, 2H), 2.21 (t, 2H, J=10.8Hz), 2.22-2.36 (m, 1H), 2.96-3.20 (m, 2H), 3.57 (d, 2H, J=12.0 Hz),3.60-3.74 (m, 1H), 6.66-6.85 (m, 2H), 6.98 (d, 1H, J=7.8 Hz), 7.47 (d,1H, J=8.7 Hz), 9.30 (s, 1H).

Ia-83

mp 118-119° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.41 (d, 6H, J=6.3 Hz), 1.26 (s,9H), 1.40-1.67 (m, 4H), 2.17-2.36 (m, 3H), 2.97-3.10 (m, 2H), 3.57 (d,2H, J=12.0 Hz), 3.61-3.74 (m, 1H), 6.67-6.92 (m, 3H), 7.48 (t, 1H, J=9.0Hz), 9.37 (s, 1H).

Ia-84

mp 265-267° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.21 (d, 6H, J=6.6 Hz), 1.20-1.57(m, 4H), 1.60-2.30 (m, 9H), 2.99-3.20 (m, 4H), 3.40-3.52 (m, 2H), 5.09(s, 1H), 6.91 (d, 2H, J=8.7 Hz), 6.98 (d, 1H, J=7.5 Hz), 7.37 (d, 2H,J=8.7 Hz), 7.42 (d, 2H, J=8.7 Hz), 7.51 (d, 2H, J=8.7 Hz), 9.56 (s, 1H).

Ia-85

mp 185-186° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.26 (s, 9H), 1.42-1.72 (m, 6H),1.96-2.10 (m, 2H), 2.26 (t, 2H, J=6.9 Hz), 2.96-3.12 (m, 4H), 3.41-3.52(m, 2H), 5.09 (s, 1H), 6.88 (d, 1H, J=8.7 Hz), 6.92 (d, 2H, J=9.0 Hz),7.37 (d, 2H, J=8.7 Hz), 7.43 (d, 2H, J=9.0 Hz), 7.52 (d, 2H, J=8.7 Hz),9.63 (s, 1H).

Ia-86

mp 162-164° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.21 (d, 6H, J=6.6 Hz), 1.41-1.73(m, 6H), 1.96-2.10 (m, 2H), 2.26 (t, 2H, J=7.2 Hz), 2.91-3.20 (m, 5H),3.42-3.52 (m, 2H), 5.09 (s, 1H), 6.92 (d, 2H, J=9.3 Hz), 6.99 (t, 1H,J=6.0 Hz), 7.37 (d, 2H, J=8.7 Hz), 7.43 (d, 2H, J=9.3 Hz), 7.52 (d, 2H,J=8.7 Hz), 9.64 (s, 1H).

Ia-87

mp 245-247° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.22 (d, 6H, J=6.6 Hz), 1.22-1.58(m, 4H), 1.81-2.02 (m, 4H), 2.22-2.36 (m, 1H), 3.00-3.20 (m, 2H), 3.01(s, 3H), 6.99 (d, 1H, J=8.4 Hz), 7.75-7.88 (m, 2H), 8.19 (d, 1H, J=1.2Hz), 10.4.3 (s, 1H).

Ia-88

mp 208-209° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.22 (d, 6H, J=6.9 Hz), 1.22-1.55(m, 4H), 1.75-1.98 (m, 4H), 2.11-2.24 (m, 1H), 2.98-3.20 (m, 2H), 5.96(s, 2H), 6.82 (d, 1H, J=8.4 Hz), 6.91-7.03 (m, 2H), 7.30 (d, 1H, J=1.8Hz), 9.72 (s, 1H).

Ia-89

mp 142-143° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.40-1.66 (m, 4H),2.26 (t, 2H, J=7.5 Hz), 3.02 (q, 2H, J=6.6 Hz), 5.96 (s, 2H), 6.82 (d,1H, J=8.4 Hz), 6.88 (t, 1H, J=8.4 Hz), 6.94 (dd, 1H, J=1.8, 8.4 Hz),7.30 (d, 1H, J=1.8 Hz), 9.78 (s, 1H).

Ia-90

mp 100° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.20 (d, 6H, J=6.9 Hz), 1.40-1.66 (m,4H), 2.26 (t, 2H, J=7.5 Hz), 2.89-2.99 (m, 2H), 3.13 (quint, 1H, J=6.6Hz), 5.96 (s, 2H), 6.83 (d, 1H, J=8.1 Hz), 6.91-7.02 (m, 2H), 7.30 (d,1H, J=1.8 Hz), 9.78 (s, 1H).

Ia-91

mp 189-190° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.26 (s, 9H), 1.43-1.71 (m, 4H),2.40 (t, 2H, J=7.5 Hz), 2.97-3.09 (m, 2H), 3.01 (s, 3H), 6.85-6.93 (m,1H), 7.76-7.88 (m, 2H), 8.20 (d, 1H, J=1.2 Hz), 10.49 (s, 1H).

Ia-104

mp 238-241° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m, 4H),1.8-2.0 (m, 4H), 2.50 (m, 1H), 3.05 (m, 1H), 6.55 (br s, 1H), 6.79 (d,1H, J=8.2), 7.15 (t, 1H, J=4.8), 8.64 (d, 2H, J=4.8 Hz).

Ia-105

mp 232-234° C. ¹H-NMR (DMSO) δ ppm: 1.26 (s, 9H), 1.2-1.5. (m, 4H),1.8-2.0 (m, 4H), 2.55 (m, 1H), 3.05 (m, 1H), 6.77 (d, 1H, J=8.7), 9.92(s, 2H), 10.93 (s, 1H).

Ia-106

mp 226-228° C. ¹H-NMR (DMSO) δ ppm: 1.28 (s, 9H), 1.22-1.58 (m, 4H),1.82-2.04 (m, 4H), 2.29 (m, 1H), 3.07 (m, 1H), 6.79 (d, 1H, J=8.7 Hz),7.61 (d-d, 1H, J=1.8 Hz, 8.7 Hz), 8.04 (d, 1H, J=8.7 Hz), 8.48 (d, 1H,2.1 Hz), 9.35 (s, 1H), 10.05 (s, 1H).

Ia-107

mp 282-283° C. ¹H-NMR (DMSO) δ ppm: 1.22-1.57 (m, 4H), 1.27 (s, 914),1.80-2.04 (m, 4H), 2.27 (m, 1H), 3.06 (m, 1H), 6.81 (d, 1H, J=8.7 Hz),7.32 (m, 1H), 7.44 (t, 2H, J=7.5 Hz), 7.57-7.72 (m, 6H), 9.91 (s, 1H).

Ia-108

mp 191-192° C. ¹H-NMR (DMSO) δ ppm: 1.24-1.58 (m, 4H), 1.28 (s, 9H),1.86-2.04 (m, 4H), 2.70 (m, 1H), 3.08 (m, 1H), 6.83 (d, 1H, J=8.7 Hz),7.63-7.79 (m, 2H), 8.31 (d, 1H, J=7.2 Hz), 10.27 (s, 1H).

Ia-109

mp 283-285° C. ¹H-NMR (DMSO) δ ppm: 1.24-1.60 (m, 4H), 1.28 (s, 9H),1.87-2.04 (m, 4H), 2.42 (m, 1H), 3.09 (m, 1H), 3.87 (s, 2H), 6.82 (d,1H, J=8.7 Hz), 7.28-7.43 (m, 3H), 7.60 (d, 2H, J=7.8 Hz), 7.68 (d, 1H,J=7.2 Hz), 7.89 (d, 1H, J=7.5 Hz), 9.48 (s, 1H).

Ia-110

mp 263-265° C. ¹H-NMR (DMSO) δ ppm: 1.24-1.54 (m, 4H), 1.27 (s, 9H),1.76-1.87 (m, 2H), 1.89-2.01 (m, 2H), 2.17 (m, 1H), 3.04 (m, 1H), 4.01(s, 4H), 6.01 (s, 2H), 6.44 (d, 2H, J=8.7 Hz), 6.77 (d, 1H, J=8.7 Hz),7.39 (d, 2H, J=9,0 Hz), 9.44 (s, 1H).

Ia-111

mp 239-241° C. ¹H-NMR (DMSO) δ ppm: 1.24-1.54 (m, 4H), 1.27 (s, 9H),1.62-1.76 (m, 4H), 1.80-2.02 (m, 4H), 2.30 (m, 1H), 2.47-2.59 (m, 2H),2.66-2.76 (m, 2H), 6.08 (m, 1H), 6.79 (d, 1H, J=9.0 Hz), 6.88 (d, 1H,J=6.9 Hz), 7.02 (t, 1H, J=7.5 Hz), 7.13 (d, 1H, J=7.5 Hz), 8.98 (s, 1H).

Ia-124

mp 247-249° C. ¹H-NMR (DMSO) δ ppm: 1.15 (d, 6H, J=6.3 Hz), 1.30 (s,9H), 2.15-2.26 (m, 2H), 3.48-3.57 (m, 2H), 3.63-3.76 (m, 2H), 6.92 (d,2H, J=8.7 Hz), 7.59 (d, 2H, J=9.0 Hz), 7.38 (d, 2H, J=9.0 Hz), 7.87 (d,2H, J=8.7 Hz), 9.92 (brs, 1H), 9.98 (brs, 1H).

Ia-125

mp 228-232° C. ¹H-NMR (DMSO) δ ppm: 1.30 (s, 9H), 1.95-2.08 (m, 2H),2.77-2.89 (m, 4H), 7.17 (d, 1H, J=8.4 Hz), 7.39 (d, 2H, J=9.0 Hz),7.42-7.48 (m, 1H), 7.64 (brs, 1H), 7.87 (d, 2H, J=9.0 Hz), 9.99 (brs,2H).

Ia-126

mp 244-246° C. ¹H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 7.42 (d, 2H, J=8.4Hz), 7.81 (d-d, 1H, J=2.1 Hz, 8.7 Hz), 7.93 (d, 2H, J=9.0 Hz), 8.05 (d,1H, J=9.0 Hz), 8.66 (d, 1H, J=2.1 Hz), 9.29 (s, 1H), 10.05 (brs, 1H),10.39 (brs, 1H).

Ia-127

mp 238-239° C. ¹H-NMR (DMSO) δ ppm: 1.30 (s, 9H), 4.18-4.27 (m, 4H),6.81 (d, 1H, J=8.4 Hz), 7.16 (d-d, 1H, J=2.7 Hz, 9.0 Hz), 7.34-7.42 (m,3H), 7.85 (d, 2H, J=8.4 Hz), 9.94 (brs, 1H), 9.99 (brs, 1H).

Ia-128

mp 286-287° C. ¹H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 7.41 (d, 2H, J=8.7Hz), 7.71 (d, 2H, J=8.4 Hz), 7.91 (d, 2H, J=8.7 Hz), 7.99 (d, 2H, J=8.7Hz), 10.05 (brs, 1H), 10.44 (brs, 1H).

Ia-129

mp 232-234° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m, 4H),1.8-2.0 (m, 4H), 2.25 (1H, m), 3.07 (m, 1H), 6.80 (d, 1H, J=9.0), 7.37(d, 1H, J=8.1), 7.53 (t, 1H, J=8.1), 7.75 (t, 1H, J=8.1), 8.12 (s, 1H),10.16 (s, 1H).

Ia-130

mp 274-277° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.23-1.58 (m, 4H),1.81-2.03 (m, 4H), 2.28 (m, 1H), 3.07 (m, 1H), 6.80 (d, 1H, J=8.4 Hz),7.36 (d-d, 1H, J=0.9 Hz, 5.7 Hz), 7.43 (d-d, 1H, J=2.1 Hz, 8.7 Hz), 7.60(d, 1H, J=5.4 Hz), 7.78 (d, 1H, J=8.7 Hz), 8.40 (d, 1H, 1.8 Hz), 9.97(brs, 1H).

Ia-131

mp 259-260° C. ¹H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 7.40 (d, 1H, J=4.8Hz), 7.41 (d, 2H, J=8.7 Hz), 7.66 (d, 1H, J=5.1 Hz), 7.67 (d-d, 1H,J=1.8 Hz, 8.7 Hz), 7.84 (d, 1H, J=9.0 Hz), 7.92 (d, 2H, J=8.7 Hz), 8.50(s, 1H), 10,03 brs, 1H), 10,27 (brs 1H).

Ia-132

mp 265-266° C. ¹H-NMR (DMSO) δ ppm: 1.17 (d, 6H, J=6.6 Hz), 1.31 (s,9H), 4.10 (m, 1H), 7.35-7.46 (m, 3H), 7.54 (d, 1H, J=7.5 Hz), 7.87-7.97(m, 3H), 8.15 brs, 1H), 8.20 (d, 1H, J=7.5 Hz), 10.03 brs, 1H), 10.25(brs, 1H).

Ia-133

mp 249-250° C. ¹H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 7.41 (d, 2H, J=8.7Hz), 7.45 (d, 1H, J=5.4 Hz), 7.67 (d-d, 1H, J=1.8 Hz, 8.7 Hz), 7.76 (d,1H, J=5.4 Hz), 7.92 (d, 2H, J=8.7 Hz), 7.95 (d, 1H, J=8.1 Hz), 8.39 (d,1H, J=1.8 Hz), 10.02 (brs, 1H), 10 23 (brs, 1H).

Ia-134

mp 305-306° C. ¹H-NMR (DMSO) δ ppm: 1.25 (m, 2H), 1.25 (s, 9H), 1.52 (m,21), 1.82 (m, 2H), 1.94 (m, 2H), 2.13 (m, 1H), 3.04 (m, 1H), 6.00 (d,1H, J=8.1), 6.74 (d, 1H, J=8.4), 7.3-7.5 (m, 6H), 7.85 (d, 2H, J=7.5),8.31 (d, 1H, J=8.4).

Ia-135

mp 220-222° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m, 4H),1.8-2.0 (m, 4H), 2.37 (m, 1H), 3.03 (m, 1H), 6.80 (d, 1H, J=8.7), 7.04(m, 1H), 7.29 (m, 1H), 7.79 (m, 1H), 9.60 (s, 1H).

Ia-136

mp 263-264° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m 4H),1.8-2.0 (m, 4H), 2.20 (m, 1H), 3.03 (m, 1H), 6.80 (d, 1H, J=8.4), 6.87(m, 1H), 7.31 (m, 2H), 10.21 (s, 1H).

Ia-137

mp 260-262° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m, 4H),1.8-2.0 (m, 4H), 2.30 (m, 1H), 3.05 (m, 1H), 6.80 (d, 1H, J=8.4), 7.13(t, 2H, J=8.1), 7.31 (m, 1H), 9.52 (s, 1H).

Ia-138

mp 270-273° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m, 4H),1.8-2.0 (m, 4H), 2.12 (m, 1H), 3.05 (m, 1H), 6.79 (d, 1H, J=9.0), 7.31(m, 2H), 7.80 (m, 1H), 10.05 (s, 1H).

Ia-139

mp 267-270° C. ¹H-NMR (DMSO) δ ppm: 1.30 (s, 9H), 4.05 (s, 4H), 6.04 (s,2H), 6.51 (d, 2H, J=8.7 Hz), 7.34 (d, 2H, J=8.4 Hz), 7.54 (d, 2H, J=8.4Hz), 7.87 (d, 2H, J=8.4 Hz), 9.82 (brs, 1H), 9.97 (brs, 1H).

Ia-140

mp 227-229° C. ¹H-NMR (DMSO) δ ppm: 1.22 (d, 6H, J=6.6 Hz), 1.20-1.57 (m4H), 1.80-2.01 (m, 4H), 2.27 (m, 1H), 2.95-3.22 (m, 2H), 6.99 (d, 1H,J=7.8 Hz), 7.65 (d, 2H, J=8.7 Hz), 7.80 (d, 2H, J=8.4 Hz), 10.18 (brs,1H).

Ia-141

mp 205-207° C. ¹H-NMR (DMSO) δ ppm: 1.22 (d, 6H, J=6.9 Hz), 1.20-1.55(m, 4H), 1.75-2.05 (m, 6H), 2.21 (m, 1H), 2.72-2.85 (m, 4H), 2.93-3.20(m, 2H), 6.98 (d, 1H, J=8.1 Hz), 7.10 (d, 1H, J=8.1 Hz), 7.26 (d-d, 1H,J=2.1 Hz, 8.1 Hz), 7.51 (s, 1H), 9.67 (brs, 1H).

Ia-142

mp 295-296° C. ¹H-NMR (DMSO) δ ppm: 1.15 (d, 6H, J=6.6), 1.27 (s, 9H),1.3-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.27 (m, 1H), 3.05 (m, 1H), 4.07 (m,1H), 6.80 (d, 1H, J=8.7), 7.64 (d, 2H, J=8.7), 7.79 (d, 2H, J=8.7), 8.06(d, 1H, J=7.5), 10.01 (s, 1H).

Ia-143

mp 146-147° C. ¹H-NMR (DMSO) δ ppm: 1.26 (s, 9H), 1.5-1.7 (m, 4H), 2.36(t, 2H, J=7.8), 3.03 (q, 2H, J=6.3), 6.89 (t, 1H, J=6.3), 7.66 (d, 2H,J=8.4), 7.80 (d, 2H, J=8.4), 10.25 (s, 1H).

Ia-144

mp 138-140° C. ¹H-NMR (DMSO) δ ppm: 1.21 (d, 6H, J=6.0), 1.4-1.7 (m,4H), 2.37 (t, 2H, J=7.5), 2.96 (q, 2H, J=6.3), 3.14 (m, 1H), 6.99 (t,1H, J=5.4), 7.66 (d, 2H, J=7.8), 7.81 (d, 2H, J=7.8), 10.25 (s, 1H).

Ia-145

mp 134-136° C. ¹H-NMR (DMSO) δ ppm: 1.26 (s, 9H), 1.39 (m, 2H), 1.4-1.7(m, 4H), 2.28 (t, 2H, J=7.2), 2.79 (m, 4H), 3.02 (q, 2H, J=7.2), 6.88(t, 1H, J=6.0), 7.10 (t, 1H, J=6.0), 7.51 (s, 1H), 9.73 (s, 1H).

Ia-146

mp 135-137° C. ¹H-NMR (DMSO) δ ppm: 1.20 (d, 6H, J=6.6), 1.4-1.7 (m,4H), 1.99 (m, 2H), 2.28 (t, 2H, J=7.2), 2.79 (m, 4H), 2.94 (q, 2H,J=6.3), 3.13 (m, 1H), 6.98 (t, 1H, J=6.9), 7.10 (d, 2H, J=8.1), 7.26 (d,2H, J=8.1), 7.51 (s, 1H), 9.73 (s, 1H).

Ia-147

mp 206-207° C. ¹H-NMR (DMSO) δ ppm: 1.29 (s, 9H), 4.54 (d, 2H, J=5.7Hz), 7.35 (d, 2H, J=9.0 Hz), 7.52 (d, 2H, J=7.8 Hz), 7.69 (d, 2H, J=8.1Hz), 7.83 (d, 2H, J=8.7 Hz), 9.02 (t, 1H, J=5.7 Hz), 9.97 (brs, 1H).

Ia-148

mp 250-251° C. ¹H-NMR (DMSO) δ ppm: 1.30 (s, 9H), 7.18 (t, 2H, J=9.3Hz), 7.40 (d, 2H, J=8.7 Hz), 7.76 (d-d, 2H, J=5.1 Hz, 9.3 Hz), 7.88 (d,2H, J=9.0 Hz), 10.02 (brs, 1H), 10.17 (brs, 1H).

Ia-149

mp 220-222° C. ¹H-NMR (DMSO) δ ppm: 1.30 (s, 9H), 3.74 (s, 3H), 6.92 (d,2H, J=9.0 Hz), 7.38 (d, 2H, J=9.0 Hz), 7.64 (d, 2H, J=9.0 Hz), 7.87 (d,2H, J=9.0 Hz), 9.99 (s, 2H).

Ia-150

mp 264-266° C. ¹H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 1.66-1.76 (m, 4H),2.57-2.66 (m, 2H), 2.71-2.80 (m, 2H), 6.98 (m, 1H), 7.06-7.16 (m, 2H),7.38 (d, 2H, J=9.0 Hz), 7.90 (d, 2H, J=8.7 Hz), 9.60 (s, 1H), 9.99 (s,1H).

Ia-151

mp 235-236° C. ¹H-NMR (DMSO) δ ppm: 1.03-1.39 (m, 5H), 1.27 (s, 9H),1.55-1.87 (m, 5H), 3.73 (m, 1H), 7.31 (d, 2H, J=8.7 Hz), 7.76 (d, 2H,J=8.4 Hz), 8.01 (d, 1H, J=7.8 Hz), 9.90 (s, 1H).

Ia-152

mp 244-246° C. ¹H-NMR (DMSO) δ ppm: 0.50-0.72 (m, 4H), 1.27 (s, 9H),2.81 (m, 1H), 7.31 (d, 2H, J=8.7 Hz), 7.73 (d, 2H, J=8.7 Hz), 8.30 (d,1H, J=4.2 Hz), 9.91 (brs, 1H).

Ia-153

mp>300° C. ¹H-NMR (DMSO) δ ppm: 1.06 (m, 6H), 1.27 (s, 9H), 1.2-1.5 (m,4H), 1.8-2.0 (m, 4H), 2.25 (m, 1H), 2.7 (m, 1H), 3.05 (m, 1H), 3.51 (m,4H), 4.30 (m, 1H), 6.80 (d, 1H, J=8.4), 7.34 (d, 2H, J=8.4), 7.65 (d,2H, J=8.4), 10.01 (s, 1H).

Ia-154

mp 247-249° C. ¹H-NMR (DMSO) δ ppm: 1.05 (m, 6H), 1.27 (s, 9H), 1.2-1.5(m, 4H), 1.8-2.0 (m, 4H), 2.23 (m, 1H), 2.77 (m, 1H), 3.05 (m, 1H), 3.52(m, 4H), 4.33 (m, 1H), 6.80 (d, 1H, J=9.0), 7.03 (d, 1H, J=7.8), 7.35(t, 1H, J=7.8), 7.59 (d, 1H, J=7.8), 7.68 (s, 1H), 9.96 (s, 1H).

Ia-155

mp 258-259° C. ¹H-NMR (DMSO) δ ppm: 1.25 (m, 2H), 1.50 (m, 2H), 1.86 (m,2H), 1.99 (m, 2H), 2.28 (m, 1H), 2.93 (s, 3H), 3.10 (m, 1H), 7.02 (d,1H, J=7.5), 7.65 (d, 2H, J=8.4), 7.80 (d, 2H, J=8.4), 10.20 (s, 1H).

Ia-156

mp 250-253° C. ¹H-NMR (DMSO) δ ppm: 1.28 (m, 2H), 1.50 (m, 2H), 1.82 (m,2H), 2.00 (m, 4H), 2.22 (m, 1H), 2.79 (m, 4H), 2.92 (s, 3H), 3.11 (m,1H), 7.01 (d, 1H, J=(0.1), 7.26 (d, 1H, J=8.1), 7.51 (s, 1H), 9.68 (s,1H).

Ia-157

mp 259-262° C. ¹H-NMR (DMSO) δ ppm: 1.13 (d, 6H, J=6.0), 1.25 (m, 2H),1.50 (m, 2H), 1.80 (m, 2H), 1.95 (m, 2H), 2.17 (m, 3H), 2.92 (s, 3H),3.10 (m, 1H), 3.70 (m, 2H), 3.68 (m, 2H), 6.86 (d, 2H J=9.3), 7.00 (d,1H, J=7.2), 7.43 (d, 2H, J=9.3), 9.58 (s, 1H).

Ia-158

mp 298-300° C. ¹H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 7.30-7.50 (m, 5H),7.63-7,71 (m, 4H), 7.87 (d, 2H, J=8.7 Hz), 7.91 (d, 2H, J=9.0 Hz), 10.03(brs, 1H), 10.22 (brs, 1H).

Ia-159

mp 278-281° C. ¹H-NMR (DMSO) δ ppm: 0.74-1.87 (m, 20H), 1.29 (s, 9H),3.76 (m, 1H), 7.32 (d, 2H, J=8.4 Hz), 7.75 (d, 2H, J=8.7 Hz), 7.75 (d,1H, J=8.7 Hz), 7.90 (brs, 1H).

Ia-160

mp 227-228° C. ¹H-NMR (DMSO) δ ppm: 1.22-1.55 (m, 4H), 1.27 (s, 9H),1.80-2.02 (m, 4H), 2.23 (m, 1H), 3.06 (m, 1H), 6.78 (d, 1H, J=8.7 Hz),7.45 (t, 1H, J=9.9 Hz), 7.82 (m, 1H), 8.12 (d-d, 1H, J=2.4 Hz, 6.3 Hz),10.17 (brs, 1H).

Ia-161

mp 259-260° C. ¹H-NMR (DMSO) δ ppm: 1.22-1.54 (m, 4H), 1.27 (s, 9H),1.78-2.01 (m, 4H), 2.16 (s, 3H), 2.21 (m, 1H), 3.05 (m, 1H), 6.77 (d,1H, J=8.4 Hz), 7.12-7.21 (m, 2H), 7.53 (m, 1H), 9.90 (brs, 1H).

Ia-162

mp 222-226° C. ¹H-NMR (DMSO) δ ppm: 1.15 (d, 6H, J=6.3 Hz), 1.26 (d, 6H,J=6.9 Hz), 2.16-2.26 (m, 2H), 3.31 (m, 1H), 3.48-3.58 (m, 2H), 3.63-3.76(m, 2H), 6.92 (d, 2H, J=9.0 Hz), 7.32 (d, 2H, J=8.7 Hz), 7.59 (d, 2H,9.0 Hz), 7.89 (d, 2H, J=9.0 Hz), 9.92 (s, 1H), 10.13 (brs, 1H).

Ia-163

mp 197-200° C. ¹-NMR (DMSO) δ ppm: 1.26 (d, 6H, J=6.3 Hz), 1.95-2.09 (m,2H), 2.77-2.90 (m, 4H), 3.32 (m, 1H), 7.17 (d, 1H, J=8.1 Hz), 7.32 (d,2H, J=8.7 Hz), 7.45 (d-d, 1H, J=1.8 Hz, 8.1 Hz), 7.64 (brs, 1H), 7.90(d, 2H, J=8.7 Hz), 9.99 (brs, 1H), 10.13 (brs, 1H).

Ia-164

mp 145-247° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-2.0 (m, 16H), 2.19(m, 1H), 3.05 (m, 1H), 4.74 (m, 1H), 6.79 (d, 1H, J=9.0), 6.80 (d, 2H,J=9.0), 7.47 (d, 2H, J=9.0), 9.63 (s, 1H).

Ia-165

mp>300° C. ¹H-NMR (DMSO) δ ppm: 1.03-2.02 (m, 18H), 1.27 (s, 9H), 2.26(m, 1H), 3.06 (m, 1H), 3.73 (m, 1H), 6.78 (d, 1H, J=8.7 Hz), 7.6:3 (d,2H, J=9.0 Hz), 7.78 (d, 2H, J=8.7 Hz), 8.02 (d, 1H, J=8.1 Hz), 10.00(brs, 1H).

Ia-166

mp 200-201° C. ¹H-NMR (DMSO) δ ppm: 1.03-2.02 (m, 18H), 1.27 (s, 9H),2.25 (m, 1H), 3.06 (m, 1H), 3.73 (m, 1H), 6.78 (d, 1H, J=8.7 Hz), 7.33(t, 1H, J=8.1 Hz), 7.46 (d, 1H, J=8.1 Hz), 7.76 (m, 1H), 7.94 (m, 1H),8.14 (d, 1H, J=8.1 Hz), 9.92 (brs, 1H).

Ia-167

mp 282-285° C. ¹H-NMR (DMSO) δ ppm: 1.22-1.57 (m, 4H), 1.27 (s, 9H),1.87-2.03 (m, 4H), 2.49 (m, 1H), 3.07 (m, 1H), 6.83 (d, 1H, J=8.7 Hz),13.20 (brs, 1H).

Ia-168

mp 120-124° C. ¹H-NMR (DMSO) δ ppm: 0.94-1.66 (m, 14H), 1.27 (s, 9H),1.80-2.04 (m, 4H), 2.25 (m, 1H), 2.92 (m, 1H), 3.06 (m, 1H), 6.78 (d,1H, J=8.7 Hz), 7.42-7.53 (m, 2H), 7.63 (d, 1H, J=7.2 Hz), 7.73 (m, 1H),8.17 (m, 1H), 10.11 (brs, 1H).

Ia-169

mp 256-257° C. ¹H-NMR (DMSO) δ ppm: 0.93-1.20 (m, 5H), 1.24-1.64 (m,9H), 1.27 (s, 9H), 1.80-2.02 (m, 4H), 2.27 (m, 1H), 2.87 (m, 1H), 3.06(m, 1H), 6.79 (d, 1H, J=9.0 Hz), 7.48 (d, 1H, J=7.2 Hz), 7.68-7.79 (m,4H), 10.17 (brs, 1H).

Ia-171

mp 242-244° C. ¹H-NMR (DMSO) δ ppm: 1.27 (m, 12H), 1.45 (m, 4H), 1.90(m, 4H), 2.25 (m, 1H), 3.07 (m, 1H), 3.67 (m, 2H), 6.77 (d, 1H, J=8.7),6.90 (d, 1H, J=7.8), 7.31 (t, 1H, J=7.5), 7.53 (d, 1H, J=7.8), 7.59 (s,1H), 9.89 (s, 1H).

Ia-172

mp>310° C. ¹H-NMR (DMSO) δ ppm: 1.27 (m, 12H), 1.38 (m, 4H), 1.84 (m,2H), 1.97 (m, 2H), 2.25 (m, 1H), 3.07 (m, 1H), 3.66 (m, 2H), 6.81 (d,1H, J=8.7), 7.20 (d, 2H, J=6.7), 7.61 (d, 2H, J=8.7), 9.94 (s, 1H).

Ia-173

mp 279-281° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m, 4H), 1.83(m, 6H), 1.93 (m, 2H), 2.21 (m, 1H), 2.36 (m, 2H), 3.05 (m, 1H), 3.54(m, 2H), 6.79 (d, 1H, J=8.7), 7.16 (d, 2H, J=9.0), 7.56 (d, 2H, J=9.0),9.83 (s, 1H).

Ia-174

mp 258-262° C. ¹H-NMR (DMSO) δ ppm: 0.29 (m, 2H), 0.53 (m, 2H), 1.20 (m,1H), 1.27 (s, 9H), 1.3-1.5 (m, 4H), 1.7-2.0 (m, 4H), 2.20 (m, 1H), 3.05(m, 1H), 3.75 (d, 2H, J=6.9), 6.79 (d, 1H, J=9.0), 6.83 (d, 2H, J=9.0),7.46 (d, 2H, J=9.0), 9.64 (s, 1H).

Ia-175

mp 246-248° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-2.0 (m, 18H), 2.19(m, 1H), 3.04 (m, 1H), 4.23 (m, 1H), 6.79 (d, 1H, J=8.7), 6.84 (d, 2H,J=9.0), 7.45 (d, 2H, J=9.0), 9.64 (s, 1H).

Ia-176

mp 200-202° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-2.0 (m, 18H), 2.21(m, 1H), 3.05 (m, 1H), 4.23 (m, 1H), 6.57 (d, 1H, J=6.9), 6.80 (d, 1H,J=9.0), 7.0-7.2 (m, 2H), 7.28 (s, 1H), 9.74 (s, 1H).

Ia-177

mp 266-268° C. ¹H-NMR (DMSO) δ ppm: 1.22-1.56 (m, 4H), 1.27 (s, 9H),1.79-2.02 (m, 4H), 2.25 (m, 1H), 3.05 (m, 1H), 6.56 (m, 1H), 6.77-6.84(m, 2H), 7.58-7.71 (m, 5H), 9.92 (brs, 1H).

Ia-178

mp 223-224° C. ¹H-NMR (DMSO) δ ppm: 1.26-1.54 (m, 4H), 1.27 (s, 9H),1.81-2.02 (m, 4H), 2.45 (m, 1H), 3.06 (m, 1H), 6.80 (d, 1H, J=8.7 Hz),8.15 (d-d, 1H, J=2.4 Hz, 9.0 Hz), 8.27 (d, 1H, J=9.0 Hz), 8.70 (m, 1H),10.85 brs, 1H).

Ia-179

mp 224-227° C. ¹H-NMR (DMSO) δ ppm: 1.24-1.56 (m, 4H), 1.27 (s, 9H),1.80-2.03 (m, 4H), 2.27 (m, 1H), 3.06 (m, 1H), 6.80 (d, 1H, J=8.7 Hz),6.90 (d, 1H, J=1.8 Hz), 7.72-7.84 (m, 4H), 8.60 (d, 1H, J=1.8 Hz), 10.09(brs, 1H).

Ia-180

mp 226-227° C. ¹H-NMR (DMSO) δ ppm: 0.92 (d, 6H, J=6.6 Hz), 1.26-1.55(m, 4H), 1.27 (s, 9H), 1.80-2.03 (m, 4H), 2.27 (m, 1H), 3.05 (m, 1H),3.20 (m, 1H), 6.80 (d, 1H, J=8.7 Hz), 7.42 (d, 1H, J=7.2 Hz), 7.67-7.79(m, 4H), 10.19 brs, 1H).

Ia-181

mp 191-192° C. ¹H-NMR (DMSO) δ ppm: 0.95 (d, 6H, J=6.6 Hz), 1.26-1.55(m, 4H), 1.27 (s, 9H), 1.80-2.03 (m, 4H), 2.25 (m, 1H), 3.06 (m, 1H),3.23 (m, 1H), 6.80 (d, 1H, J=8.4 Hz), 7.41-7.53 (m, 2H), 7.58 (d, 1H,J=7.2 Hz), 7.73 (m, 1H), 8.18 (m, 1H), 10.13 (brs, 1H).

Ia-182

mp 192-193° C. ¹H-NMR (DMSO) δ ppm: 0.30 (m, 2H), 0.55 (m, 2H), 1.2-1.5(m, 5H), 1.27 (s, 1H), 1.8-2.0 (m, 4H), 2.20 (m, 1H), 3.04 (m, 1H), 3.75(d, 2H, J=6.9), 6.58 (m, 1H), 6.79 (d, 1H, J=8.7), 7.0-7.2 (m, 2H), 7.31(s, 1H), 9.76 (s, 1H).

Ia-183

mp>310° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m, 4H), 1.82 (m,2H), 1.97 (m, 2H), 2.04 (m, 2H), 2.39 (m, 1H), 2.46 (t, 2H, J=7.8), 3.07(m, 1H), 3.79 (t, 2H, J=7.5), 6.79 (d, 1H, J=8.7), 7.56 (m, 4H), 9.80(s, 1H).

Ia-184

mp 281-283° C. ¹H-NMR DMSO) δ ppm: 1.24-1.57 (m, 4H), 1.27 (s, 9H),1.80-2.04 (m, 4H), 2.27 (m, 1H), 3.06 (m, 1H), 6.80 (d, 1H, J=9,0 Hz),7.33 (s, 1H), 7.75 (d, 2H, J=9.3 Hz), 7.91 (d, 2H, J=8.7 Hz), 8.16 (s,1H), 10.09 (brs, 1H).

Ia-185

mp 226-227° C. ¹H-NMR (DMSO) δ ppm: 1.24-1.58 (m, 10H), 1.27 (s, 9H),1.81-2.02 (m, 4H), 2.28 (m, 1H), 2.78-2.88 (m, 4H), 3.06 (m, 1H), 6.80(d, 1H, J=8.7 Hz), 7.64 (d, 2H, J=8.7 Hz), 7.82 (d, 2H, J=8.7 Hz), 10.25brs, 1H).

Ia-186

mp 148-150° C. ¹H-NMR (DMSO) δ ppm: 1.25-1.60 (m, 10H), 1.27 (s, 9H),1.82-2.03 (m, 4H), 2.24 (m, 1H), 2.82-2.92 (m, 4H), 3.06 (m, 1H), 6.79(d, 1H, J=8.4 Hz), 7.36 (m, 1H), 7.55 (t, 1H, J=7.8 Hz), 7.84 (m, 1H),8.06 (m, 1H), 10.18 (brs, 1H).

Ia-187

mp>310° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.36 (s, 9H), 1.43 (m,4H), 1.85 (m, 2H), 1.93 (m, 2H), 2.27 (m, 1H), 3.06 (m, 1H), 6.80 (d,1H, J=8.7), 7.58 (s, 1H), 7.62 (d, 2H), 7.75 (d, 2H, J=9.0), 10.00 (s,1H).

Ia-188

mp 285-292° C. ¹H-NMR (DMSO) δ ppm: 0.85 (t, 3H, J=7.5), 1.11 (d, 3H,J=6.3), 1.26 (s, 9H), 1.3-1.6 (m, 6H), 1.85 (m, 2H), 1.95 (m, 2H), 2.27(m, 1H), 3.06 (m, 1H), 3.90 (m, 1H), 6.80 (d, 1H, J=8.4), 7.64 (d, 2H,J=8.7), 7.79 (d, 2H, J=8.7), 7.99 (d, 1H, J=8.1), 10.02 (s, 1H).

Ia-189

mp 278-281° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.2-2.0 (m, 17H), 2.03(m, 2H), 3.03 (m, 1H), 6.79 (d, 1H, J=8.4), 7.1-7.3 (m, 3H), 7.94 (s,1H), 9.78 (m, 2H).

Ia-190

mp>310° C. ¹H-NMR (DMSO) δ ppm: 1.1-2.0 (m, 17H), 1.27 (s, 9H), 2.25 (m,2H), 3.03 (m, 1H), 6.79 (d, 1H, J=8.7), 7.48 (m, 4H), 9.71 (m, 2H).

Ia-191

mp 275-277° C. ¹H-NMR (DMSO) δ ppm: 1.16 (d, 6H, J=6.6 Hz), 1.31 (s,9H), 4.09 (m, 1H), 7.41 (d, 2H, J=8.7 Hz), 7.84 (s, 4H), 7.90 (d, 2H,J=9.0 Hz), 8.11 (d, 1H, J=7.5 Hz), 10.04 (brs, 1H), 10.30 (brs, 1H).

Ia-192

mp 204-205° C. ¹H-NMR (DMSO) δ ppm: 1.15 (d, 6H, J=6.6 Hz), 1.20-1.56(m, 4H), 1.22 (d, 6H, J=6.6 Hz), 1.78-2.00 (m, 4H), 2.25 (m, 1H),2.98-3.22 (m, 2H), 4.06 (m, 1H), 6.99 (d, 1H, J=8.1 Hz), 7.34 (t, 1H,J=8.1 Hz), 7.46 (d, 1H, J=7.8 Hz), 7.75 (m 1H), 7.96 (m, 1H), 8.17 (d,1H, J=8.7 Hz), 9.94 (brs, 1H).

Ia-193

mp 285-286° C. ¹H-NMR (DMSO) δ ppm: 1.15 (d, 6H, J=6.6 Hz), 1.20-1.56(m, 4H), 1.22 (d, 6H, J=6.9 Hz), 1.79-2.00 (m, 4H), 2.26 (m, 1H),2.97-3.20 (m, 2H), 4.07 (m, 1H), 6.99 (d, 1H, J=7.8 Hz), 7.64 (d, 2H,J=8.7 Hz), 7.79 (d, 2H, J=8.7 Hz), 8.06 (d, 1H, J=7.5 Hz), 10.02 (brs,1H).

Ia-194

mp 248-250° C. ¹H-NMR (DMSO) δ ppm: 1.22-1.57 (m, 4H), 1.22 (d, 6H,J=6.6 Hz), 1.78-2.00 (m, 4H), 2.25 (m, 1H), 2.98-3.22 (m, 2H), 6.56 (m,1H), 6.82 (d, 1H, J=3.3 Hz), 6.99 (d, 1H, J=7.8 Hz), 7.58-7.71 (m, 5H),9.92 brs, 1H).

Ia-195

mp 271-275° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.28-1.56 (m, 4H),1.80-2.02 (m, 4H), 2.25 (m, 1H), 3.06 (m, 1H), 6.80 (d, 1H, J=9.0 Hz),7.57 (s, 1H), 7.62-7.74 (m, 4H), 8.39 (s, 1H), 9.99 (brs, 1H).

Ia-196

mp 226-228° C. ¹H-NMR (CDCl₃) δ ppm: 0.30 (m, 2H), 1.23 (d, 6H, J=6.9),1.2-2.0 (m, 4H), 2.20 (m, 1H), 3.10 (m, 2H), 3.76 (d, 2H, J=6.9), 6.83(d, 2H, J=8.7), 6.99 (d, 1H, J=8.1), 7.46 (d, 2H, J=8.7), 9.65 (s, 1H).

Ia-197

mp 173-175° C. ¹H-NMR (DMSO) δ ppm: 0.31 (m, 2H), 0.56 (m, 2H), 1.22 (d,6H, J=6.6), 1.2-1.5 (m, 4H), 1.8-2.0 (m, 4H), 2.22 (m, 1H), 3.10 (m,1H), 3.76 (d, 1H, J=7.2), 6.58 (d, 1H, J=8.1), 7.0-7.2 (m, 2H), 7.32 (s,1H), 9.78 (s, 1H).

Ia-198

mp 233-235° C. ¹H-NMR (DMSO) δ ppm: 1.25 (d, 6H, J=6.9), 1.2-2.0 (m,16H), 2.19 (m, 1H), 3.10 (m, 2H), 4.73 (m, 1H), 6.80 (d, 2H, J=8.7),6.98 (d, 1H, J=7.8), 7.45 (d, 2H, J=8.7), 9.63 (s, 1H).

Ia-199

mp 185-186° C. ¹H-NMR (DMSO) δ ppm: 1.22 (d, 6H, J=6.9), 1.2-2.0 (m,16H), 2.22 (m, 1H), 3.10 (m, 2H), 4.73 (m, 1H), 6.54 (m, 1H), 7.0-7.2(m, 2H), 7.3 (s, 1H), 9.75 (s, 1H).

Ia-200

mp 235-237° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1;6 (m, 6H),1.8-2.0 (m, 6H), 2.20 (m, 1H), 3.05 (m, 1H), 3.45 (m, 2H), 3.82 (m, 2H),4.47 (m, 1H), 6.79 (d, 1H, J=9.0), 6.89 (d, 2H, J=9.0), 7.47 (d, 2H,J=9.0), 9.66 (s, 1H).

Ia-201

mp 300-301° C. ¹H-NMR (DMSO) δ ppm: 1.15 (d, 6H, J=6.6 Hz), 1.26-1.56(m, 4H), 1.27 (s, 9H), 1.82-2.03 (m, 4H), 2.23 (s, 3H), 2.37 (m, 1H),3.06 (m, 1H), 4.07 (m, 1H), 6.81 (d, 1H, J=8.7 Hz), 7.52 (d, 1H, J=8.4Hz), 7.62 (d, 1H, J=8.4 Hz), 7.68 (s, 1H), 8.09 (d, 1H, J=7.5), 9.22(brs, 1H).

Ia-202

mp 269-270° C. ¹H-NMR (DMSO) δ ppm: 1.25-1.26 (m, 4H), 1.27 (s, 9H),1.80-2.03 (m, 4H), 2.25 (m, 1H), 3.07 (m, 1H), 6.80 (d, 1H, J=8.4 Hz),7.11 (m, 1H), 7.42 (d, 1H, J=3.6 Hz), 7.48 (m, 1H), 7.58 (d, 2H, J=8.7Hz), 7.64 (d, 2H, J=8.4 Hz), 9.92 (brs, 1H).

Ia-203

mp 271-273° C. ¹H-NMR (DMSO) δ ppm: 1.14-1.54 (m, 9H), 1.26 (s, 9H),1.63-1.88 (m, 7H), 1.89-2.01 (m, 2H), 2.21 (m, 1H), 2.42 (m, 1H), 3.04(m, 1H), 6.79 (d, 1H, J=9.0 Hz), 7.11 (d, 2H, J=8.4 Hz), 7.47 (d, 2H,J=8.1 Hz), 9.70 (brs, 1H).

Ia-204

mp 250-251° C. ¹H-NMR (DMSO) δ ppm: 1.22-1.39 (m, 2H), 1.22 (d, 6H,J=6.6 Hz), 1.40-1.57 (m, 2H), 1.80-2.01 (m, 4H), 2.28 (m, 1H), 2.98-3.21(m, 2H), 7.00 (d, 1H, J=7.8 Hz), 7.34 (s, 1H), 7.75 (d, 2H, J=9.0 Hz),7.91 (d, 2H, J=8.7 Hz), 8.17 (s, 1H), 10.10 (brs, 1H).

Ia-205

mp 239-240° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.2-1.5 (m, 4H),1.8-2.0 (m, 5H), 2.08 (m, 2H), 3.05 (m, 1H), 3.80 (m, 4H), 4.95 (m, 1H),6.79 (d, 1H, J=8.7), 6.83 (d, 2H, J=8.7), 7.48 (d, 2H, J=8.7), 9.66 (s,1H).

Ia-206

mp 236-2:38° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.2-1.7 (m, 8H),1.8-2.0 (m, 6H1), 2.18 (m, 1H), 3.04 (m, 1H), 3.3-3.6 (m, 2H), 3.85 (m,3H), 6.80 (d, 1H, J=9.0), 6.84 (d, 2H, J=9.0), 7.47 (d, 2H, J=9.0), 9.65(s, 1H).

Ia-207

mp 224-226° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.2-1.5 (m, 4H),1.8-2.0 (m, 4H), 2.24 (m, 1H), 2.39 (m, 2H), 3.06 (m, 1H), 3.50 (t, 2H,J=7.5), 3.70 (t, 2H, J=6.3), 6.78 (d, 1H, J=6.6), 6.83 (m, 1H), 7.25 (m,1H), 7.27 (m, 1H), 7.54 (s, 1H), 9.61 (s, 1H).

Ia-208

mp 275-277° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.3-1.5 (m, 4H),1.8-2.0 (m, 4H), 2.22 (m, 1H), 2.38 (m, 2H), 3.07 (m, 1H), 3.47 (t, 2H,J=6.9), 3.69 (t, 2H, J=6.6), 6.80 (d, 1H, J=8.7), 7.14 (d, 2H, J=8.4),7.58 (d, 2H, J=8.4), 9.83 (s, 1H).

Ia-209

mp 214-215° C. ¹H-NMR (DMSO) δ ppm: 1.26-1.56 (m, 4H), 1.27 (s, 9H),1.80-2.03 (m, 4H), 2.25 (m, 1H), 3.06 (m, 1H), 6.59 (m, 1H), 6.81 (d,1H, J=8.4 Hz), 6.86 (d, 1H, J=2.7 Hz), 7.28-7.40 (m, 2H), 7.47 (m, 1H),7.75 (s, 1H), 8.01 (s, 1H), 9.91 (brs, 1H).

Ia-210

mp 272-275° C. ¹H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 6.59 (m, 1H), 6.87 (d,1H, J=3.3 Hz), 7.41 (d, 2H, J=8.7 Hz), 7.68 (d, 2H, J=8.7 Hz), 7.72 (m,1H), 7.83 (d, 2H, J=8.7 Hz), 7.90 (d, 2H, J=8.7 Hz), 10.03 (brs, 1H),10.22 (brs, 1H).

Ia-211

mp 251-255° C. ¹H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 7.36 (s, 1H), 7.41 (d,2H, J=8.4 Hz), 7.91 (d, 2H, J=8.4 Hz), 7.92-8.00 (m, 4H), 8.19 (s, 1.H),10.06 (brs, 1H), 10.38 (brs, 1H).

Ia-212

mp 241-244° C. ¹H-NMR (DMSO) δ ppm: 1.30 (s, 9H), 1.50-1.78 (m, 6H),1.81-1.97 (m, 2H), 4.78 (m, 1H, 6.87 (d, 2H, J=9.0 Hz), 7.38 (d, 2H,J=8.7 Hz), 7.61 (d, 2H, J=9.0 Hz), 7.87 (d, 2H, J=8.7 Hz), 9.97 (brs,1H), 9.99 (brs, 1H).

Ia-213

mp 283-286° C. ¹H-NMR (DMSO) δ ppm: 1.31 (s, 9H), 7.12 (d-d, 1H, J=3.6Hz, 5.1 Hz), 7.41 (d, 2H, J=9.0 Hz), 7.46 (m, 1H), 7.50 (d-d, 1H, J=1.2Hz, 5.1 Hz), 7.64 (d, 2H, J=8.7 Hz), 7.82 (d, 2H, J=8.7 Hz), 7.90 (d,2H, J=9.3 Hz), 10.03 (brs, 1H), 10.22 (brs, 1H).

Ia-216

mp 224-225° C. ¹H-NMR (CDCl₃) δ ppm: 1.22 (d, 6H, J=6.9), 1.2-1.5 (m,4H), 1.8-2.0 (m, 4H), 2.45 (m, 1H), 3.12 (m, 2H), 6.99 (d, 1H, J=8.1),8.15 (m, 1H), 8.27 (d, 1H, J=9.0), 8.69 (s, 1H), 10.86 (s, 1H).

Ia-219

mp 270-272° C. ¹H-NMR (DMSO) δ ppm: 1.28 (s, 9H), 1.34-1.51 (m, 2H),1.80-1.92 (m, 2H), 2.83-2.97 (m, 2H), 3.32 (m, 1H), 3.99-4.12 (m, 2H),6.92 (d, 1H, J=8.7 Hz), 7.57 (d, 2H, J=8.7 Hz), 7.68 (d, 2H, J=9.0 Hz),8.90 (brs, 1H).

Ia-220

mp 187-189° C. ¹H-NMR (DMSO) δ ppm: 1.28 (s, 9H), 1.31-1.51 (m, 2H),1.78-1.90 (m, 2H), 2.78-2.93 (m, 2H), 3.30 (m, 1H), 3.97-4.09 (m, 2H),6.90 (d, 1H, J=8.7 Hz), 7.06 (t, 2H, J=9.0 Hz), 7.44 (d-d, 2H, J=4.8 Hz,9.0 Hz), 8.53 (brs, 1H).

Ia-221

mp 260-262° C. ¹H-NMR (DMSO) δ ppm: 1.12-1.50 (m, 7H), 1.28 (s, 9H),1.63-1.90 (m, 7H), 2.40 (m, 1H), 2.76-2.91 (m, 2H), 3.28 (m, 1H),3.96-4.09 (m, 2H), 6.90 (d, 1H, J=8.7 Hz), 7.06 (d, 2H, J=8.4 Hz), 7.32(d, 2H, J=8.4 Hz), 8.40 brs, 1H).

Ia-222

mp 265-267° C. ¹H-NMR (DMSO) δ ppm: 1.23 (d, 6H, J=6.6 Hz), 1.31-1.48(m, 2H), 1.77-1.90 (m, 2H), 2.84-2.98 (m, 2H), 3.16 (m, 1H), 3.33 (m,1H), 3.96-4.10 (m, 2H), 7.11 (d, 1H, J=7.8 Hz), 7.57 (d, 2H, J=8.7 Hz),7.67 (d, 2H, J=8.4 Hz), 8.90 (brs, 1H).

Ia-223

mp 183-186° C. ¹H-NMR (DMSO) δ ppm: 1.23 (d, 6H, J=6.9 Hz), 1.28-1.47(m, 2H), 1.76-1.88 (m, 2H, 2.80-3.16 (m, 2H), 3.16 (m, 1H), 3.32 (m,1H), 3.94-4.07 (m, 2H), 7.00-7.14 (m, 3H), 7.44 (d-d, 2H, J=4.8 Hz, 9.0Hz), 8.53 (brs, 1H).

Ia-224

mp 232-234° C. ¹H-NMR (DMSO) δ ppm: 1.12-1.46 (m, 7H), 1.23 (d, 6H,J=6.6 Hz), 1.63-1.87 (m, 7H), 2.40 (m, 1H), 2.78-2.93 (m, 2H), 3.15 (m,1H), 3.31 (m, 1H), 3.94-4.07 (m, 2H), 7.06 (d, 2H, J=8.4 Hz), 7.09 (d,1H, J=8.1 Hz), 7.32 (d, 2H, J=8.4 Hz), 8.39 brs, 1H).

Ia-225

mp 222-224° C. ¹H-NMR (DMSO) δ ppm: 1.28 (s, 9H), 1.30-1.61 (m, 4H),1.77-1.98 (m, 4H), 2.66-2.90 (m, 2H), 3.28 (m, 1H), 3.40-3.50 (m, 2H),3.79-3.88 (m, 2H), 3.96-4.08 (m, 2H, 4.44 (m, 1H), 6.85 (d, 2H, J=9.0Hz), 6.91 (d, 1H, J=9.07), 7.31 (d, 2H, J=9.3 Hz), 8.34 (brs, 1H).

Ia-226

mp 194-195° C. ¹H-NMR (CDCl₃/DMSO) δ ppm: 1.39 (d, 6H, J=7.2 Hz), 1.66(quintet, 2H, J=6.8 Hz), 1.87 (quintet, 2H, J=7.7 Hz), 2.47 (t, 2H,J=7.5 Hz), 3.11-3.22 (m, 1H), 3.21 (t, 2H, J=6.2 Hz), 5.00 (brs, 1H),7.35-7.56 (m, 5H), 7.86 (d, 1H, J=8.4 Hz), 8.05 (dd, 1H, J=1.8, 8.1 Hz),8.20 (d, 1H, J=1.8 Hz), 9.24 (s, 1H).

Ia-227

mp>300° C. ¹H-NMR (DMSO) δ ppm: 1.22 (d, 6H, J=6.3 Hz), 1.20-1.40 (m,4H), 1.74-2.10 (m, 4H), 2.20-2.40 (m, 1H), 2.39 (s, 3H), 3.00-3.30 (m,2H), 6.25 (s, 1H), 6.99 (brs, 1H), 7.43-7.57 (m, 1H), 7.71 (d, 1H, J=8.1Hz), 7.76 (s, 1H), 10.27 (s, 1H).

Ia-228

mp 168-169° C. ¹H-NMR (DMSO) δ ppm: 1.26 (s, 9H), 1.49 (quintet, 2H,J=7.5 Hz), 1.64 (quintet, 2H, J=7.4 Hz), 2.38 (t, 2H, J=7.2 Hz), 2.40(s, 3H), 3.04 (q, 2H, J=6.5 Hz), 6.25 (s, 1H), 6.89 (t, 1H, J=6.0 Hz),7.48 (dd, 1H, J=1.8, 8.4 Hz), 7.71 (d, 1H, J=8.4 Hz), 7.77 (d, 1H, J=1.8Hz), 10.33 (s, 1H).

Ia-229

mp 174-175° C. ¹H-NMR (DMSO) δ ppm: 1.21 (d, 6H, J=6.6 Hz), 1.42-1.56(m, 2H), 1.56-1.70 (m, 2H), 2.33-2.42 (m, 2H), 2.40 (s, 3H), 2.90-3.02(m, 2H), 3.14 (septet, 1H, J=6.5 Hz), 6.26 (s, 1H), 6.99 (brs, 1H), 7.48(d, 1H, J=8.4 Hz), 7.71 (d, 1H, J=8.7 Hz), 7.77 (s, 1H), 10.33 (s, 1H).

Ia-230

mp 194-195° C. ¹H-NMR (DMSO) δ ppm: 0.86 (d, 6H, J=6.9 Hz), 1.25-1.65(m, 4H), 1.27 (s, 9H), 1.81-2.05 (m, 5H), 2.23-2.35 (m, 1H), 2.99-3.15(m, 1H), 3.36 (d, 2H, J=7.2 Hz), 6.80 (d, 1H, J=8.4 Hz), 7.80 (d, 1H,J=8.4 Hz), 7.87 (d, 1H, J=8.4 Hz), 8.19 (s, 1H), 10.44 (s, 1H).

Ia-231

mp 221-222° C. ¹H-NMR (DMSO) δ ppm: 0.86 (d, 6H, J=6.9 Hz), 1.22-1.40(m, 2.H), 1.23 (d, 6H, J=6.9 Hz), 1.40-1.58 (m, 2H), 1.82-2.04 (m, 5H),2.22-2.37 (m, 1H), 3.00-3.16 (m, 1H), 3.15 (septet, 1H, J=6.6 Hz), 3.36(d, 2H, J=7.5 Hz), 6.99 (d, 1H, J=7.5 Hz), 7.80 (d, 1H, J=8.4 Hz), 7.86(d, 1H, J=8.4 Hz), 8.19 (s, 1H), 10.45 (s, 1H).

Ia-232

mp 196-197° C. ¹H-NMR (CDCl₃) δ ppm: 0.93 (d, 6H, J=6.6 Hz), 1.42 (s,1H), 1.60-1.70 (m, 2H), 1.88 (quintet, 2H, J=7.4 Hz), 2.02-2.20 (m, 1H),2.46 (t, 2H, J=7.7 Hz), 3.29 (q, 2H, J=6.1 Hz), 3.48 (d, 2H, J=7.8 Hz),4.26 (t, 1H, J=6.0 Hz), 7.76 (d, 1H, J=8.1 Hz), 7.90 (dd, 1H, J=1.8,8.1Hz), 8.07 (d, 1H, J=1.5 Hz), 8.39 (s, 1H).

Ia-233

mp 151-152° C. ¹H-NMR (CDCl₃) δ ppm: 0.93 (d, 6H, J=6.6 Hz), 1.40 (d,6H, J=6.6 Hz), 1.62-1.69 (m, 2H), 1.88 (quintet, 2H, J=7.3 Hz),2.03-2.16 (m, 1H), 2.47 (t, 2H, J=7.5 Hz), 3.21 (septet, 1H, J=6.8 Hz),3.23 (q, 2H, J=6.3 Hz), 3.48 (d, 2H, J=7.5 Hz), 4.43 (t, 1H, J=6.0 Hz),7.76 (d, 1H, J=8.4 Hz), 7.91 (dd, 1H, J=1.8, 8.4 Hz), 8.06 (d, 1H, J=1.8Hz), 8.36 (s, 1H).

Ia-234

mp 219-220° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.28 (s, 9H), 1.30-1.50 (m, 2H),1.74-1.88 (m, 2H), 2.83 (t, 2H, J=11.1 Hz), 3.20-3.32 (m, 1H), 3.94-4.07(m, 2H), 5.94 (s, 2H), 6.77 (d, 1H, J=8.8 Hz), 6.82 (dd, 1H, J=1.8, 8.7Hz), 6.89 (d, 1H, J=8.7 Hz), 7.11 (d, 1H, J=1.8 Hz), 8.38 (s, 1H).

Ia-235

mp 280-282° C. ¹H-NMR (DMSO-d₆) δ ppm: 1.27 (s, 9H), 1.26-1.57 (m, 4H),1.86-2.03 (m, 4H), 2.38-2.50 (m, 1H), 3.00-3.14 (m, 1H), 6.81 (d, 1H,J=8.4 Hz), 7.29 (t, 1H, J=8.4 Hz), (t, 1H, J=7.5 Hz), 7.73 (d, 1H, J=8.4Hz), 7.96 (d, 1H, J=7.5 Hz), 12.27 (s, 1H).

Ia-237

mp 204-205° C. ¹H-NMR (DMSO) δ ppm: 1.23 (d, 6H, J=6.6 Hz), 1.29-1.61(m, 4H), 1.75-1.98 (m, 4H), 2.78-2.92 (m, 2H), 3.15 (m, 1H), 3.29 (m,1H), 3.38-3.51 (m, 2H), 3.78-3.89 (m, 2H), 3.94-4.06 (m, 2H), 4.44 (m,1H), 6.85 (d, 2H, J=9.0 Hz), 7.10 (d, 1H, J=7.8 Hz), 7.31 (d, 2H, J=9.3Hz), 8.34 (brs, 1H).

Ia-238

mp 128-130° C. ¹H-NMR DMSO) δ ppm: 1.26 (s, 9H), 1.41-1.53 (m, 2H),1.55-1.68 (m, 2H), 2.44 (t, 2H, J=7.2 Hz), 2.98-3.07 (m, 2H), 6.90 (t,1H, J=6.0 Hz), 8.16 (d-d, 1H, J=2.1 Hz, 8.7 Hz), 8.29 (d, 1H, J=8.7 Hz),8.70 (m, 1H), 10.91 brs, 1H).

Ia-239

mp 256-258° C. ¹H-NMR (DMSO) δ ppm: 1.26-1.53 (m, 4H), 1.26 (s, 9H),1.76-2.00 (m, 4H), 2.23 (s, 3H), 2.39 (m, 1H), 3.04 (m, 1H), 6.80 (d,1H, J=8.7 Hz), 7.57 (d-d, 1H, J=2.4 Hz, 8.4 Hz), 7.97 (d, 1H, J=8.4 Hz),8.12 (m, 1H), 10.26 (brs, 1H).

Ia-240

mp 288-290° C. ¹H-NMR (DMSO) δ ppm: 1.26-1.53 (m, 4H), 1.27 (s, 9H),1.78-1.90 (m, 4H), 2.40 (m, 1H), 3.04 (m, 1H), 6.81 (d, 1H, J=8.7 Hz),7.07 (m, 1H), 7.75 (m, 1H), 8.07 (d, 1H, J=8.4 Hz), 8.29 (m, 1H), 10.36brs, 1H).

Ia-241

mp 249-250° C. ¹H-NMR (DMSO) δ ppm: 1.28 (s, 9H), 1.34-1.50 (m, 2H),1.79-1.90 (m, 2H), 2.74-2.98 (m, 2H), 3.32 (m, 1H), 4.02-4.14 (m, 2H),6.91 (d, 1H, J=8.4 Hz), 7.94 (d, 1H, J=9.0 Hz), 8.04 (d-d, 1H, J=2.1 Hz,9.0 Hz), 8.60 (s, 1H), 9.76 (brs, 1H).

Ia-242

mp 250-252° C. ¹H-NMR (DMSO) δ ppm: 1.24 (s, 9H), 1.27 (s, 9H),1.24-1.54 (m, 4H), 1.76-1.88 (m, 2H), 1.90-2.01 (m, 2H), 2.21 (m, 1H),3.05 (m, 1H), 6.79 (d, 1H, J=8.7 Hz), 6.88 (d, 2H, J=9.0 Hz), 7.48 (d,2H, J=9.0 Hz), 9.72 (brs, 1H).

136-0290

mp 250-252° C. ¹H-NMR (DMSO) δ ppm: 1.15 (d, 6H, J=6.6 Hz), 1.28 (s,9H), 1.35-1.52 (m, 2H), 1.78-1.92 (m, 2H), 2.20 (s, 3), 2.81-2.96 (m,2H), 3.33 (m, 1H), 3.96-4.16 (m, 3H), 6.92 (d, 1H, J=8.7 Hz), 7.27 (d,1H, J=8.1 Hz), 7.60 (m, 1H), 7.66 (m, 1H), 8.06 (d, 1H, J=7.8 Hz), 8.14(brs, 1H).

Ia-244

mp 211-213° C. ¹H-NMR DMSO) δ ppm: 1.29 (s, 9H), 1.35-1.52 (m, 2H),1.81-1.93 (m, 2H), 2.83-2.97 (m, 2), 3.32 (m, 1H), 4.03-4.14 (m, 2H),6.93 (d, 1H, J=8.7 Hz), 7.55 (d-d, 1H, J=2.1 Hz, 9.0 Hz), 7.94 (d, 1H,J=9.0 Hz), 8.29 (d, 1H, J=1.8 Hz), 8.78 (brs, 1H), 9.19 (s, 1H).

Ia-245

mp 196-197° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.2-1.6 (m, 6H),1.8-2.0 (m, 6H), 2.23 (m, 1H), 3.05 (m, 1H), 3.73 (m, 4h), 4.99 (s, 1H),6.79 (d, 1H, J=8.7), 7.1:3 (d, 1H, J=6.8), 7.22 (t, 1H, J=6.8), 7.49 (d,1H, J=6.8), 7.72 (s, 1H), 9.78 (s, 1H).

Ia-246

mp 242-244° C. ¹H-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.2-1.5 (m, 4H), 1.65(m, 4H), 1.8-2.0 (m, 4H), 2.23 (m, 1H), 2.71 (m, 1H), 3.06 (m, 1H), 3.43(m, 2H), 3.93 (m, 2H), 6.79 (d, 1H, J=8.7), 6.91 (d, 1H, J=8.7), 7.20(t, 1H, J=7.5), 7.40 (d, 1H, J=7.5), 7.5:3 (s, 1H), 9.76 (s, 1H).

Ia-247

mp 242-245° C. ¹-NMR (DMSO) δ ppm: 1.27 (s, 9H), 1.2-1.6 (m, 6H),1.8-2.0 (m, 6H), 2.23 (m, 1H), 3.05 (m, 1H), 3.74 (m, 4H), 4.94 (brs,1H), 6.79 (d, 1h, J=8.7), 7.38 (d, 1H, J=8.7), 7.52 (d, 1H, J=8.7), 9.76(s, 1H).

Ia-248

mp 272-274° C. ¹H-NMR (CDCl₃) δ ppm: 1.27 (s, 9H), 1.2-1.5 (m, 4H), 1.62(m, 4H), 1.8-2.0 (m, 4H), 2.22 (m, 1H), 2.68 (m, 1H), 3.05 (m, 1H), 3.41(m, 2H), 3.92 (m, 2H), 6.79 (d, 1H, J=9.0), 7.15 (d, 2H, J=8.7), 7.50(d, 2H, J=8.7), 9.73 (s, 1H).

Ia-249 mp 174-176° C.

Ia-250 mp 255-257° C.

Ia-252 mp 249-251° C.

Ia-253 mp 120-121° C.

Ia-254 mp 236-237° C.

Ia-255 mp 172-174° C.

Ia-256 mp 257-259° C.

Ia-257 mp 179-180° C.

Ia-258 mp 227-229° C.

Ia-259 mp 135-136° C.

Experiment 1 Affinity for NPY Y5 Receptor

cDNA sequence encoding a human NPY Y5 receptor (WO96/16542) was clonedin the expression vector pME18S (Takebe et al. Mol. Cell. Biol. 8,8957). The obtained expression vector was transfected into a host CHOcells by using a Lipofect AMINE reagent (Trademark, Gico BRL Co., Ltd.)according to an instruction protocol to obtain the cells that stablyexpress NPY Y5 receptor.

The membranes prepared from the above CHO cells expressing NPY Y5receptor, the compound of the present invention and 30,000 cpm [¹²⁵I]peptide YY (60 pM of final concentration: Amersham) were incubated inthe assay buffer (20 mM HEPES-Hanks buffer containing 0.1% bovine serumalbumin, pH 7.4) at 25° C. for 2 hours, and then the mixture wasfiltered with a glassfilter GF/C treated with polyethyleneimine. Afterthe glassfilter was washed with 50 mM Tris-HCl buffer (pH 7.4), theradioactivity on the filter was measured with a gamma counter. Thenon-specific binding was detected in the presence of 200 nM of peptideYY. The 50% inhibitory concentration of the test compound against thespecific peptide YY binding (IC₅₀ value) was calculated (Inui, A. et al.Endocrinology 131, 2090-2096 (1992)). The results are shown in Tables 1and 2.

The compounds of the present invention inhibited the binding of peptideYY (NPY homologue) to NPY Y5 receptors. In other words, the compounds ofthe present invention showed affinity for the NPY Y5 receptor.

Experiment 2 cAMP Production Inhibitory Activity in CHO Cells

After CHO cells expressing human NPY Y5 receptor were incubated in thepresence of 2.5 mM isobutylmethylxanthine (SIGMA) at 37° C. for 20 min,the compound of the present invention was added and incubated for 5 min.Then, 50 nM NPY and 10 μM forskolin (SIGMA) were added to the cells andincubated for 30 min. After the reaction was terminated by adding 1NHCl, the amount of cAMP in the supernatant was measured with EIA kit(Amersham LIFE SCIENCE). The inhibitory activity of NPY againstforskolin stimulated cAMP was regarded as 100% and the 50% inhibitoryconcentration (IC₅₀ value) of the compound of the present inventionagainst the NPY activity was calculated. The results are shown in Tables1 to 4.

TABLE 1 binding cAMP Compound IC₅₀ (nM) IC₅₀ (nM) I-2 7.5 72 I-7 3 <10I-11 1.3 5 I-18 4.4 29 I-20 7 21 I-22 8.6 51 I-24 9.6 71 I-25 0.6 2.6I-41 5.3 38.2 I-44 1.0 13.4 I-45 1.2 27.9 I-46 0.8 10.5 I-47 0.6 14.9I-49 0.4 8.1 I-50 0.3 8.4 I-53 4.1 21 I-55 9.0 40 I-57 4.8 47 I-59 0.835 I-60 0.69 18 I-61 0.26 5.3 I-62 0.58 16 I-63 1.3 50 I-64 2.2 80 I-651.8 72 I-66 1.5 30 I-67 2 17 I-69 3.8 13 I-72 2.3 2.1 I-75 0.55 3.4 I-760.61 5.5 I-77 1.8 28 I-79 0.59 25 I-83 0.61 29 I-84 1.3 25 I-86 3.4 100I-87 0.66 21 I-90 2.8 50 I-92 7 61 I-101 3.9 38 I-102 1.7 14 I-106 6.429

TABLE 2 I-109 1.2 3.2 I-110 4.3 13.6 I-111 1.8 6.1 I-114 7 30 I-116 1.211 I-120 1.4 4.8 I-123 1.8 168 I-126 0.6 13.2 I-127 1.4 30.4 I-128 1.310.2 I-129 2.1 174 I-130 1.1 42.5 I-131 1.1 34.8 I-132 2.2 30.4 I-1330.9 21.1 I-134 0.5 10.0 I-135 0.7 22.0 I-136 2.8 — I-137 1.4 68.2 I-1381.0 18.6 I-139 0.41 7.6 I-140 0.48 8.9 I-141 0.42 7.4 I-142 0.49 28I-143 3.5 44 I-144 3.4 52 I-146 2.3 20 I-147 7.1 63 I-149 0.83 15 I-1500.17 5.2 I-151 0.17 2.6 I-152 0.88 46 I-153 1.7 29 I-154 1.1 11 I-1560.81 17 I-160 0.61 8.8 I-161 0.49 3.1 I-162 1.7 32 I-163 2.3 83 I-1640.71 5.9 I-165 0.44 47 I-166 0.37 9.7 I-167 0.72 39 I-168 2.1 32 I-1712.4 71 I-172 0.91 36 I-187 0.58 13 I-191 1.1 11 I-196 1.4 6.8 I-197 6.738 I-198 7.2 33 I-199 4.8 31 I-202 6.7 67 I-204 1.0 6.3 I-205 2.9 17I-206 5.9 54 I-207 4.6 23 I-210 1.1 13 I-212 0.67 7.5 I-213 0.44 4.0Ia-1 4.8 31 Ia-3 9.2 150 Ia-4 1.4 15 Ia-5 1.6 43 Ia-6 2.4 23 Ia-8 2.9 34Ia-9 0.94 11 Ia-10 0.47 2.7 Ia-11 0.64 7.2 Ia-12 0.94 5.5 Ia-13 1.5 3.3Ia-14 4.8 28 Ia-16 0.1 — Ia-17 0.1 1.9 Ia-20 4.9 100

TABLE 3 Ia-21 3.4 35 Ia-22 3.1 38 Ia-24 5.2 74 Ia-25 1.1 18 Ia-26 1.9 27Ia-28 5.2 130 Ia-29 1 7.3 Ia-30 2.6 25 Ia-31 3.8 11 Ia-32 0.52 6.7 Ia-331.8 64 Ia-35 1.8 — Ia-36 1.6 86 Ia-37 0.73 3.8 Ia-38 1 2.2 Ia-39 1.5 3.5Ia-40 2.2 9.3 Ia-41 2.5 9 Ia-42 3.6 20 Ia-44 4.8 27 Ia-45 4.8 42 Ia-460.87 8.3 Ia-47 0.82 3.8 Ia-48 1.2 6.1 Ia-49 2.6 83 Ia-50 1.7 24 Ia-511.3 3.4 Ia-52 1.9 22 Ia-53 0.22 8.1 Ia-54 0.44 9 Ia-55 1.1 27 Ia-56 2.396 Ia-57 0.93 31 Ia-58 2.5 110 Ia-59 0.71 16 Ia-60 0.95 10 Ia-61 0.68 19Ia-62 1.1 29 Ia-63 3.9 370 Ia-64 7.1 96 Ia-65 1.1 11 Ia-66 0.59 3.2Ia-67 6.3 75 Ia-68 9.5 180 Ia-69 2.7 33 Ia-70 1.5 31 Ia-71 1.3 12 Ia-762.2 — Ia-78 2 150 Ia-79 0.82 — Ia-80 0.44 3.0 Ia-81 2.7 4.5 Ia-83 1.2 53Ia-84 0.25 13 Ia-85 0.22 14 Ia-86 0.73 11 Ia-87 0.49 61 Ia-88 0.62 48Ia-91 4 150 Ia-106 1.9 24 Ia-107 0.14 1.3 Ia-109 0.6 3.9 Ia-110 0.3 1.1Ia-111 5.1 28 Ia-124 1.1 22 Ia-125 4.1 46 Ia-126 2.3 58 Ia-127 6.1 160Ia-129 1.3 26 Ia-130 0.21 3 Ia-131 1.3 17 Ia-132 2.8 76 Ia-133 1.7 8.8Ia-135 8.2 49 Ia-136 1.6 13 Ia-138 2.2 28 Ia-139 1.9 25 Ia-140 1 24Ia-141 1 5.7 Ia-142 0.67 5.5

TABLE 4 Ia-143 7.8 39 Ia-144 6.1 57 Ia-145 7 86 Ia-146 9.9 79 Ia-1580.71 1.7 Ia-160 0.76 140 Ia-161 1.9 18 Ia-163 7 400 Ia-164 0.38 4.7Ia-168 0.95 13 Ia-169 1.9 88 Ia-173 6.9 140 Ia-174 0.35 5.4 Ia-175 0.499.2 Ia-176 0.63 5.1 Ia-177 0.49 7.5 Ia-178 4.6 16 Ia-179 0.89 19 Ia-1801.9 11 Ia-181 7.7 25 Ia-182 0.24 2.1 Ia-183 1.9 7.8 Ia-184 0.38 — Ia-1850.94 4.4 Ia-l86 0.93 12 Ia-187 1.9 60 Ia-188 0.75 28 Ia-189 3.5 95Ia-190 0.34 1000 Ia-191 0.49 220 Ia-192 5.9 200 Ia-193 1.4 43 Ia-1940.22 8.1 Ia-195 1.4 31 Ia-196 0.39 1.3 Ia-197 0.44 2.5 Ia-198 0.23 2.6Ia-199 0.11 1.6 Ia-200 1.4 18 Ia-201 3.1 74 Ia-202 0.37 3.4 Ia-203 0.22.6 Ia-204 1 6.3 Ia-205 2.4 99 Ia-206 1.9 460 Ia-207 0.55 5.9 Ia-208 1.29.7 Ia-209 0.55 — Ia-210 2.8 99 Ia-211 4.8 240 Ia-212 0.52 2.6 Ia-2130.91 28 Ia-219 2.5 28 Ia-221 0.47 1.5 Ia-222 3.7 18 Ia-224 0.1 1.2Ia-225 3.4 20 Ia-226 0.37 21 Ia-227 0.59 — Ia-228 0.96 — Ia-229 1.9 —Ia-230 0.32 — Ia-231 0.29 — Ia-232 0.7 — Ia-233 0.63 — Ia-235 5.5 —Ia-237 1.1 15 Ia-241 1.9 — Ia-243 1.3 — Ia-246 0.26 20 Ia-247 0.79 31Ia-248 0.27 17 Ia-250 1.9 — Ia-252 1.2 — Ia-253 0.53 — Ia-254 2.0 —Ia-255 3.2 — Ia-256 5.7 — Ia-257 8.6 — Ia-258 1.8 —

As shown in Tables 1 to 4, the compounds of the present invention havean NPY Y5 receptor antagonistic activity.

Experiment 3

Using the membranes prepared from Y1-expression cells (humanneuroblastoma, SK-N-MC) and the membranes prepared from Y2-expressioncells (human neuroblastoma, SMS-KAN), the experiment was carried out ina similar way as Experiment 1 to determine the affinity for NPY Y1receptor and NPY Y2 receptor.

Binding IC₅₀ values for NPY Y1 and NPY Y2 receptors of I-27, I-32, I-41,I-45, I-46, I-47, I-48, I-49, I-59, I-61, I-63, I-64, I-66, I-69, I-72,I-152, I-154, I-204, I-205, I-212, Ia-3, Ia-5, Ia-6, Ia-12, Ia-16,Ia-17, Ia-20, Ia-21, Ia-22, Ia-26, Ia-28, Ia-29, Ia-30, Ia-31, Ia-32,Ia-33, Ia-37, Ia-39, Ia-40, Ia-50, Ia-51, Ia-54, Ia-62, Ia-67, Ia-124,Ia-126, Ia-139, Ia-140, Ia-142, Ia-178, Ia-199 and Ia-200 were 100,000nM or higher and each compound had a selectivity for NPY Y5 receptor.

Formulation Example 1 Tablets

Compound (I-1) 15 mg Starch 15 mg Lactose 15 mg Crystalline cellulose 19mg Polyvinyl alcohol  3 mg Distilled water 30 ml Calcium stearate  3 mg

After all of the above ingredients except for calcium stearate areuniformly mixed, the mixture is crushed and granulated, and dried toobtain a suitable size of granules. After calcium stearate is added tothe granules, tablets are formed by compression molding.

Formulation Example 2 Capsules

Compound (I-2) 10 mg Magnesium stearate 10 mg Lactose 80 mg

After the above ingredients are mixed to prepare powders or granules,the obtained are filled in capsules.

Formulation Example 3 Granules

Compound (I-3)  30 g Lactose 265 g Magnesium Stearate  5 g

After the above ingredients are mixed uniformly and formed bycompression molding, the obtained are crushed, granulated and sieved toprepare suitable volume of granules.

Industrial Applicability

As shown in the above Experiments, the compounds of the presentinvention have an NPY Y5 receptor antagonistic activity. Therefore, thecompounds of the present invention are useful as an anti-obestic agentand anorectic agent.

What is claimed is:
 1. A pharmaceutical composition comprising atherapeutically effective amount of a compound of the formula (I):

wherein R¹ is optionally substituted lower alkyl, optionally substitutedcycloalkyl or optionally substituted aryl, R² is hydrogen or loweralkyl, and R¹ and R² taken together may form lower alkylene, n is 1 or2, R³, R⁴, R⁵ and R⁶ are each independently hydrogen or lower alkyl,

 is optionally substituted cycloalkylene or optionally substitutedbicycloalkylene, and p and q are each independently 0 or 1, R⁷ ishydrogen or lower alkyl, and Z is optionally substituted pyridyl,prodrug, pharmaceutically acceptable salt or hydrate thereof togetherwith a pharmaceutically acceptable carrier.
 2. The pharmaceuticalcomposition claimed in claim 1 wherein R² is hydrogen or lower alkyl. 3.The pharmaceutical composition claimed in claim 1 wherein R¹ isoptionally substituted lower alkyl or optionally substituted cycloalkyl,and p and q are
 0. 4. The pharmaceutical composition claimed in any oneof claims 1 to 3 wherein R¹ is optionally substituted C3 to C10 alkyl.5. The pharmaceutical composition claimed in any one of claims 1 to 3which is an anti-obestic agent.
 6. The pharmaceutical compositionclaimed in any one of claims 1 to 3 which is an anorectic agent.
 7. Amethod for treating obesity comprising administering to a subject thatis obese an effective dose of the pharmaceutical composition claimed inany one of claims 1 to
 3. 8. A method for suppressing food intakecomprising administering to a subject that is obese an effective dose ofthe pharmaceutical composition claimed in any one of claims 1 to
 3. 9. Acompound of the formula (I);

wherein R¹ is optionally substituted C3 to C10 alkyl or optionallysubstituted C5 to C6 cycloalkyl and the other symbols are the same asdefined in claim 1, prodrug, pharmaceutically acceptable salt or hydratethereof.
 10. The compound described in claim 9 wherein

is optionally substituted cyclohexylene and p and q are simultaneously0, prodrug, pharmaceutically acceptable salt or hydrate thereof.